1. Context
Oxytocin, often referred to as the “love hormone,” is well known for its involvement in childbirth, breastfeeding, and social bonding. It plays a critical role during pregnancy by helping to lower blood pressure and promote relaxation. At the time of delivery, oxytocin stimulates uterine contractions, aiding in the childbirth process. During postpartum breastfeeding, oxytocin facilitates milk flow by causing the milk ducts in the breasts to contract. In some cases, artificial oxytocin is administered during labour to aid in the progression of delivery and prevent excessive bleeding after the placenta is separated [1].
Beyond its traditional reproductive functions, oxytocin has gained attention for its broader physiological effects. It is increasingly recognized as a key regulator of the immune system. Produced in the hypothalamus and secreted by the pituitary gland, oxytocin has been shown to interact with immune cells, cytokines, and inflammatory mediators, suggesting it has immune-modulatory effects that extend beyond social behaviour and emotional regulation [2].

2. Evidence Acquisition
Recent research has expanded our understanding of oxytocin’s role in immune system regulation. The hormone has been shown to influence immune responses, particularly in the context of inflammation, autoimmune diseases, and chronic conditions [3]. Oxytocin’s impact on the immune system involves complex signaling mechanisms, which include direct activation of immune cells and indirect modulation via neuroendocrine and psychosocial pathways. Its effects on immune cells such as T cells, B cells, macrophages, and dendritic cells are well documented, though the specific mechanisms underlying these interactions remain under investigation [4].
Among its most significant effects is oxytocin’s ability to modulate the inflammatory response. This has important implications for chronic inflammatory diseases, neuro-inflammatory conditions, and autoimmune disorders, with oxytocin’s anti-inflammatory effects helping to reduce the production of pro-inflammatory cytokines [5]. Furthermore, the interplay between oxytocin, immune function, stress, and mental health underscores the importance of understanding the neuroimmune interactions it facilitates.
While the role of oxytocin in immune regulation is becoming clearer, the genetic and molecular processes behind this link remain poorly understood. Advancing this understanding requires genetic research into oxytocin receptor (OXTR) polymorphisms and their effects on immune function, as well as the involvement of oxytocin in regulating immune-related gene expression. Variations in the OXTR gene have been associated with changes in immune response, social behaviours, and susceptibility to autoimmune disorders, making it essential to investigate how genetic predispositions may influence the effects of oxytocin on immune modulation [6].
In addition to genetic insights, developments in omics technologies—such as transcriptomics, proteomics, and metabolomics—have provided a more comprehensive understanding of oxytocin’s effects on cellular signalling networks, gene expression, and immune regulation. These technologies enable high-throughput studies that reveal the molecular pathways through which oxytocin influences gene expression, protein activity, and metabolic changes, offering deeper insights into its role in immune function [7].

2.1. Aim of the study
This study’s objective is to present a comprehensive, up-to-date review of the literature on the connection between oxytocin and the immune system, with an emphasis on the molecular and genetic processes at play. The effects of oxytocin on immune system elements, such as cytokine modulation, inflammatory pathways, and immune cell activity, will be investigated in this study. Additionally, it will investigate the genetic resources linked to oxytocin signalling, such as receptor gene polymorphisms, and the potential effects of these genetic variables on the immunological response. In order to assess the possible therapeutic uses of oxytocin in the treatment of autoimmune illnesses, chronic inflammation, and immunological dysfunction, the study will also take into account findings from current preclinical and clinical research. Through the synthesis of current research findings and the identification of existing gaps, this study seeks to provide guidance for future research and therapeutic applications while also deepening our understanding of oxytocin’s involvement in immune modulation.

3. Molecular and Genetic Mechanisms
To comprehend oxytocin’s wider physiological functions, it is essential to comprehend the molecular and genetic processes that underlie its impact on the immune system. These methods include the activation of intricate biochemical pathways that control immunological responses, the interaction of oxytocin with certain receptors, and the genetic regulation of its synthesis. Furthermore, oxytocin signalling and its effects on immune system control are modulated by epigenetic changes. The main genetic and molecular elements that control how oxytocin interacts with the immune system are described in this section [4, 8].

3.1. Oxytocin receptors: Structure and function
By attaching itself to certain receptors called oxytocin receptors (OXTRs), which are G-protein-coupled receptors (GPCRs), oxytocin produces its effects [9]. The extensive expression of these receptors in a variety of organs, such as the brain, uterus, mammary glands, and immune cells, emphasizes the vast range of physiological functions of oxytocin. The seven transmembrane domains that make up the oxytocin receptor’s structure allow it to engage with external ligands like oxytocin and start intracellular signalling [10]. When OXTRs bind to oxytocin, they initiate downstream signalling cascades, mainly by activating phospholipase C (PLC), which causes the synthesis of diacylglycerol (DAG) and inositol triphosphate (IP3) [11]. The intracellular calcium (Ca2+) levels rise as a result of these second messengers, activating a number of proteins and enzymes involved in cellular reactions. This route is essential for controlling the cytokine synthesis, cell division, and proliferation of immune cells. The direct role of oxytocin in immune system regulation is highlighted by the presence of OXTRs on immune cells such T lymphocytes, dendritic cells, and macrophages. Further evidence that the effects of oxytocin are very context-dependent comes from the variety of oxytocin receptor isoforms and their tissue-specific expression patterns. According to recent studies, OXTR gene alternative splicing can result in differences in receptor function, which may affect how oxytocin interacts with immune cells under various physiological circumstances, including autoimmune disorders and infections [12].

3.2. Genetic regulation of oxytocin production
Genetic regulation of oxytocin production and release is quite strict. The human chromosome 3 contains the OXTR gene, which is the main gene that codes for oxytocin. The prepro-oxytocin protein is produced by this gene and then cleaved into the active oxytocin peptide. Numerous elements, including hormone signals, neurotransmitters, and environmental cues, affect how the OXTR gene is expressed [13]. At the genetic level, promoter regions and transcription factors that regulate the gene’s transcription in response to particular physiological situations might alter the expression of the OXTR gene [14]. For instance, cortisol levels under stress might change OXTR expression, which in turn affects the body’s capacity to use oxytocin to control immunological responses. 
Furthermore, single nucleotide polymorphisms (SNPs), which are genetic variations in the OXTR gene, have been linked to differences in the expression and function of the oxytocin receptor. These variations may have an impact on an individual’s immune response, social behaviours, and susceptibility to diseases. The oxytocin-neurophysin I gene, which codes for the precursor molecule of oxytocin and its carrier protein, neurophysin, also affects the control of oxytocin production. Immune function may be impacted by variations in oxytocin levels caused by variations in this gene’s expression. The intricacy of oxytocin’s function in the immune system is highlighted by the complicated control of its synthesis, which includes both genetic and hormonal factors [15].

3.3. Molecular pathways involved in oxytocin and immunity
By modulating the MAPK pathway, oxytocin can influence the production of inflammatory cytokines, such as interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), which are central to the immune response during infection and inflammation [16]. Additionally, oxytocin has been shown to modulate the NF-κB pathway, a crucial regulator of immune cell activation and the inflammatory response. Oxytocin’s ability to inhibit NF-κB activation in certain immune cells suggests that it may exert an anti-inflammatory effect, which could have therapeutic implications in conditions characterized by excessive inflammation, such as autoimmune diseases and neuroinflammatory disorders [17]. By regulating these pathways, oxytocin can fine-tune immune responses, promoting an appropriate immune reaction while preventing excessive inflammation that could lead to tissue damage. Oxytocin also interacts with T-helper cells (Th cells) and macrophages, influencing their differentiation and cytokine production [18]. For example, oxytocin has been shown to enhance the Th2 response, which is associated with anti-inflammatory effects and the resolution of inflammation. This interaction highlights oxytocin’s role in balancing immune responses, ensuring that they are not overly aggressive, which could lead to autoimmunity [19].

3.4. Epigenetic modulation of oxytocin signaling
Epigenetic mechanisms, including DNA methylation, histone modification, and non-coding RNA regulation, also play a crucial role in modulating oxytocin signalling and its effects on the immune system. Changes in the epigenetic regulation of oxytocin-related genes can affect their expression and ultimately influence immune responses. For example, DNA methylation in the promoter regions of the OXTR gene has been associated with reduced receptor expression, which may result in a diminished ability to modulate immune responses through oxytocin signalling [20]. Histone modifications, such as acetylation and methylation, can also influence the transcriptional activity of oxytocin-related genes, affecting their expression in response to environmental cues such as stress or inflammation. These modifications can have lasting effects on immune system function, contributing to an individual’s susceptibility to immune-related diseases. Additionally, the regulation of oxytocin receptor expression by long non-coding RNAs (lncRNAs) and microRNAs (miRNAs) represents another layer of epigenetic control, offering potential targets for therapeutic intervention [21].
The epigenetic regulation of oxytocin signalling is particularly relevant in the context of environmental exposures that may influence gene expression [22]. For instance, early-life stressors can lead to epigenetic modifications of the OXTR gene, resulting in altered oxytocin signalling and potentially contributing to long-term immune system dysregulation. Understanding how epigenetic factors influence oxytocin signalling will provide deeper insights into how environmental and genetic factors combine to shape immune system function [22].

4. Oxytocin and the Immune System: Cellular Interactions
The relationship between oxytocin and the immune system is a complex interplay that involves the direct interaction of oxytocin with various immune cells and its modulation of immune responses [4]. Oxytocin’s ability to influence immune cell function, inflammatory pathways, and the secretion of cytokines and chemokines has significant implications for health and disease. This section delves into the cellular interactions of oxytocin with immune cells, its role in modulating inflammatory responses, its influence on cytokine and chemokine regulation, and its potential involvement in autoimmune diseases [23].

4.1. Oxytocin’s effect on immune cells
Oxytocin exerts a direct effect on several immune cell types, including T lymphocytes, macrophages, dendritic cells, and B cells. These cells express oxytocin receptors (OXTRs), allowing oxytocin to influence their function and behaviour. One of the primary effects of oxytocin on immune cells is its ability to regulate cell differentiation, activation, and cytokine production [4].
T cells: Oxytocin modulates the activity of T-helper (Th) cells, influencing the immune response. Studies have shown that oxytocin can promote the differentiation of Th2 cells, which are associated with anti-inflammatory cytokine production, such as IL-4, and reduce the differentiation of Th1 cells, which are involved in pro-inflammatory responses. This shift in T-cell balance suggests that oxytocin plays a role in regulating immune tolerance and reducing excessive immune activation [5].
Macrophages and dendritic cells: Oxytocin affect macrophage polarization, promoting an M2 macrophage phenotype, which is generally associated with tissue repair and anti-inflammatory responses. Additionally, oxytocin has been shown to influence dendritic cell function, which is crucial for antigen presentation and the activation of T cells. By modulating the activation of these immune cells, oxytocin can help regulate immune responses to pathogens or injury while minimizing excessive inflammation [24].
B cells: In B cells, oxytocin has been found to affect antibody production. While the exact mechanism remains unclear, evidence suggests that oxytocin may enhance B-cell activation and differentiation, which could influence the production of antibodies during immune responses. This effect may be particularly relevant in the context of immune challenges, such as infections or vaccination [25].

4.2. Immune modulation by oxytocin in inflammatory responses
Oxytocin has been shown to play a significant role in modulating the body’s inflammatory response. Inflammation is a key feature of many immune-related conditions, including infections, autoimmune diseases, and chronic inflammatory disorders [26]. Oxytocin’s ability to modulate inflammation occurs through several mechanisms:
Cytokine regulation: Oxytocin can influence the production of pro-inflammatory and anti-inflammatory cytokines. It has been shown to inhibit the release of pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, which are typically elevated in inflammatory responses. Conversely, oxytocin can stimulate the release of anti-inflammatory cytokines, including IL-10, which helps to resolve inflammation and promote tissue repair [17].
Activation of anti-inflammatory pathways: One of the major pathways involved in the anti-inflammatory effects of oxytocin is the inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway. NF-κB is a critical regulator of inflammation, and its activation leads to the production of pro-inflammatory mediators. By inhibiting NF-κB, oxytocin may help prevent excessive or chronic inflammation, which is often seen in autoimmune diseases and inflammatory conditions [27].
Stress-induced inflammation: Chronic stress is known to increase inflammation, and oxytocin’s ability to modulate the stress response plays an important role in controlling stress-induced inflammatory reactions. Oxytocin’s effects on the hypothalamic-pituitary-adrenal (HPA) axis and its ability to reduce cortisol levels contribute to its anti-inflammatory properties. This stress-modulatory effect suggests that oxytocin may be particularly important in regulating inflammation in individuals under chronic stress or those with stress-related disorders [28].

4.3. Interaction of oxytocin with cytokines and chemokines
Cytokines and chemokines are key signalling molecules that regulate immune cell communication and orchestrate the immune response to infections, injuries, or other pathological conditions [29]. Oxytocin interacts with both cytokines and chemokines to modulate immune responses:
Cytokine modulation: As mentioned earlier, oxytocin can inhibit the release of pro-inflammatory cytokines like TNF-α, IL-1β, and IL-6. These cytokines are often elevated in conditions such as autoimmune diseases, infections, and inflammatory disorders [17]. By reducing the production of these pro-inflammatory cytokines, oxytocin helps to prevent excessive inflammation and tissue damage. Moreover, oxytocin has been shown to enhance the production of anti-inflammatory cytokines, including IL-10, promoting a more balanced immune response and reducing the risk of chronic inflammation [5].
Chemokine regulation: Chemokines are signalling proteins that guide the migration of immune cells to sites of infection or injury. Oxytocin has been implicated in regulating the production of certain chemokines, such as C-C motif ligand 2 (CCL2), which is involved in recruiting immune cells to inflammatory sites [30]. By modulating chemokine expression, oxytocin can influence immune cell trafficking, ensuring that immune cells are directed appropriately in response to immune challenges [30]..
Cytokine-chemokine interplay: The interaction between cytokines and chemokines is crucial for the coordination of immune responses. Oxytocin’s ability to regulate both cytokine and chemokine production suggests that it plays a broader role in fine-tuning immune system activation and maintaining immune homeostasis. This dual modulation could be particularly important in the context of immune-related diseases, where dysregulated cytokine and chemokine signalling contribute to disease progression [31].

4.4. Role of oxytocin in autoimmune diseases
Autoimmune diseases occur when the immune system mistakenly targets the body’s own cells, leading to chronic inflammation and tissue damage. The role of oxytocin in autoimmune diseases is an emerging area of research, with evidence suggesting that oxytocin may help regulate the immune system in ways that prevent or mitigate autoimmune responses.
Regulation of immune tolerance: Oxytocin’s ability to shift the balance between Th1 and Th2 responses is particularly relevant in autoimmune diseases. Th1 responses, which are associated with the production of pro-inflammatory cytokines, are typically involved in autoimmune attacks, while Th2 responses promote anti-inflammatory effects. Oxytocin’s modulation of this balance may help prevent excessive Th1-driven inflammation and promote immune tolerance, reducing the risk of autoimmunity [32].
Multiple sclerosis (MS): One autoimmune disease, where oxytocin has shown potential therapeutic effects, is MS, a condition in which the immune system attacks the central nervous system. Studies have suggested that oxytocin administration can reduce the severity of MS symptoms by promoting an anti-inflammatory environment and regulating immune cell activity. This effect is thought to be mediated by oxytocin’s ability to modulate the activity of microglia (resident immune cells in the brain) and T cells [33].
Rheumatoid arthritis (RA): Another autoimmune disorder that may benefit from oxytocin’s immune-modulatory effects is RA, a disease characterized by joint inflammation and immune cell infiltration. Research has indicated that oxytocin’s anti-inflammatory effects may help alleviate symptoms of RA by reducing the production of pro-inflammatory cytokines and promoting the resolution of inflammation [34].
Systemic lupus erythematosus (SLE): SLE is an autoimmune disease where the immune system attacks various organs. Oxytocin’s regulation of cytokine production and immune cell activation may play a role in modulating the immune dysregulation that occurs in SLE. Studies have indicated that oxytocin’s anti-inflammatory properties may help reduce the severity of SLE symptoms by balancing the immune response [35].

5. Oxytocin and Inflammation
Oxytocin, traditionally known for its roles in childbirth, lactation, and social bonding, is increasingly recognized for its influence on inflammation and immune responses [36]. Inflammatory processes are central to various disease states, and oxytocin’s ability to modulate these processes opens up new therapeutic avenues. 

5.1. The impact of oxytocin on inflammatory pathways
Inflammation is a complex biological response to injury, infection, or harmful stimuli, involving immune cell activation, cytokine release, and changes in vascular permeability. Oxytocin exerts significant influence on these pathways by interacting with immune cells and modulating key inflammatory mediators [37].
NF-κB pathway inhibition: One of the primary mechanisms by which oxytocin regulates inflammation is through the inhibition of the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathway [17]. NF-κB is a major transcription factor involved in the expression of pro-inflammatory cytokines and is activated in response to a variety of stressors. By inhibiting NF-κB, oxytocin reduces the production of inflammatory cytokines such as TNF-α, IL-1β, and IL-6, thus preventing excessive inflammatory responses [38].
MAPK/ERK pathway modulation: Oxytocin also affects the mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK) signalling pathway, which plays a crucial role in immune cell activation and cytokine production. Through activation of this pathway, oxytocin can modulate the immune response by influencing immune cell differentiation and cytokine release. This helps fine-tune the body’s response to pathogens, injury, or other immune challenges [5].
Reduction in oxidative stress: Oxytocin has been shown to reduce oxidative stress, which is often associated with inflammation. By regulating the activity of antioxidant enzymes, oxytocin helps to limit the damage caused by reactive oxygen species (ROS) during inflammatory processes. This antioxidant effect may contribute to its ability to protect tissues from damage during inflammation [39].
Modulation of immune cell function: Oxytocin can influence the activation and polarization of various immune cells, including T lymphocytes, macrophages, and dendritic cells. Through its interaction with these cells, oxytocin can promote the release of anti-inflammatory cytokines such as IL-10, while inhibiting pro-inflammatory cytokine production. This balancing act helps to control the immune response and prevent excessive inflammation [5].

5.2. Oxytocin as a potential therapeutic agent in inflammation
Given its ability to regulate immune responses and modulate inflammatory pathways, oxytocin has emerged as a potential therapeutic agent for a variety of inflammation-related conditions. Its natural anti-inflammatory properties make it an attractive candidate for managing diseases characterized by chronic inflammation or autoimmune dysfunction.
Autoimmune diseases: As discussed in previous sections, oxytocin’s ability to modulate the balance between Th1 and Th2 immune responses makes it a promising therapeutic candidate for autoimmune diseases. By promoting an anti-inflammatory Th2 response and inhibiting the pro-inflammatory Th1 response, oxytocin could help reduce the severity of autoimmune attacks and tissue damage. Conditions such as MS, RA, and SLE may benefit from oxytocin-based therapies aimed at restoring immune balance [40].
Chronic inflammatory conditions: Chronic inflammation is a hallmark of numerous conditions, including asthma, inflammatory bowel disease (IBD), and cardiovascular diseases. Oxytocin’s ability to reduce the production of pro-inflammatory cytokines and modulate immune cell activity could help mitigate the progression of these diseases. In particular, oxytocin’s anti-inflammatory effects on macrophages and T cells may provide relief from the persistent inflammation seen in these conditions [41].
Neuroinflammation: Oxytocin’s role in modulating the blood-brain barrier (BBB) and its anti-inflammatory effects on microglial cells are of particular interest in the context of neuro-inflammatory diseases such as Alzheimer’s disease (AD), Parkinson’s disease, and MS. Neuroinflammation is a central feature of these disorders, and oxytocin’s ability to regulate microglial activation and reduce oxidative stress could have therapeutic potential in alleviating neurodegenerative symptoms [42].
Post-surgical inflammation: Inflammatory responses following surgery are common and can delay healing and increase the risk of complications. Oxytocin’s anti-inflammatory effects could be useful in post-surgical recovery, helping to reduce the inflammatory response and promote faster healing. Studies investigating the use of oxytocin in post-operative care are still in their early stages, but early results are promising [43]. To provide a clearer overview of the therapeutic applications, dosages, models, and outcomes, a summary of preclinical and clinical studies on oxytocin’s role in inflammation-related disorders is presented in Table 1.

5.3. Inflammation-related disorders and oxytocin
Several case studies and preclinical studies have explored the potential of oxytocin as a therapeutic agent in inflammation-related disorders. These case studies demonstrate oxytocin’s capacity to modulate inflammation and provide insights into its clinical applications.
MS: In a preclinical mouse model of MS, oxytocin administration resulted in a significant reduction in the severity of symptoms, likely due to its ability to suppress pro-inflammatory cytokine production and shift the immune response towards a more anti-inflammatory profile. These findings suggest that oxytocin could be used as a treatment to mitigate the neuroinflammation seen in MS [44].
RA: In a study examining the effects of oxytocin on RA, oxytocin treatment was shown to reduce joint inflammation and the production of pro-inflammatory cytokines in animal models. By promoting an anti-inflammatory Th2 response, oxytocin helped to alleviate symptoms associated with RA, such as pain and swelling. These findings support the idea that oxytocin may be beneficial in treating chronic inflammatory conditions like RA [45].
IBD: In an animal model of colitis, a form of IBD, oxytocin administration was shown to reduce intestinal inflammation and improve the overall health of the digestive tract. The anti-inflammatory effects of oxytocin were linked to its ability to modulate immune cell function and inhibit the release of inflammatory cytokines. This study highlights the potential of oxytocin in treating gastrointestinal inflammatory disorders [46].

6. Oxytocin and Immune System Dysfunction
Oxytocin, as a regulator of both the nervous and immune systems, plays a crucial role in maintaining immune homeostasis. However, dysregulation of oxytocin signalling can lead to immune system dysfunction, contributing to the development of various chronic diseases and immune deficiencies. This section explores the consequences of oxytocin dysregulation on immune responses, its role in chronic diseases and immune deficiency, and the potential for oxytocin-based therapies in restoring immune balance.

6.1. Dysregulation of oxytocin and immune imbalance
The balance of immune system activity is crucial for maintaining health. Dysregulation of oxytocin, whether through receptor malfunction, altered expression levels, or disrupted signalling pathways, can contribute to immune imbalances. Such imbalances may manifest in either excessive immune activation or immune suppression, both of which are linked to a range of disorders [47].
Decreased oxytocin levels: A reduction in oxytocin levels has been implicated in various diseases marked by immune dysregulation. In particular, low oxytocin levels can lead to heightened inflammatory responses. The inability to properly modulate immune cell activity may contribute to chronic inflammation, which is a hallmark of many autoimmune and inflammatory diseases [42]. Studies have shown that individuals with conditions such as RA, MS, and chronic IBD may have lower oxytocin levels, suggesting that insufficient oxytocin signalling could exacerbate these conditions.
Impaired oxytocin receptor function: The functional disruption of oxytocin receptors (OXTRs) can also result in immune dysfunction. The reduced sensitivity or expression of OXTRs on immune cells can hinder oxytocin’s ability to regulate cytokine production and immune cell activation. This dysfunction may lead to an unbalanced immune response, where pro-inflammatory pathways dominate, potentially triggering or worsening autoimmune reactions [4].
Chronic stress and oxytocin dysregulation: Chronic stress is a significant factor in oxytocin dysregulation. Prolonged exposure to stress hormones, such as cortisol, can inhibit oxytocin production and receptor function, disrupting its immune-modulatory effects. Stress-induced oxytocin deficiency has been associated with immune dysfunction, where the lack of appropriate immune suppression can contribute to conditions like inflammation, autoimmune disease, and immune deficiency. The bidirectional relationship between stress and immune system dysfunction highlights the importance of maintaining proper oxytocin signalling for immune health [28].

6.2. The role of oxytocin in chronic diseases and immune deficiency
Oxytocin plays an integral role in the immune response, and its dysregulation is associated with several chronic diseases and conditions marked by immune system dysfunction. The peptide’s involvement in inflammation, immune tolerance, and the regulation of immune cell activation makes it crucial in the pathogenesis of a variety of chronic diseases and immune deficiencies [17].
Chronic inflammatory diseases: Chronic diseases such as RA, SLE, asthma, and IBD are characterized by persistent inflammation and immune system dysfunction. Dysregulated oxytocin signalling has been linked to exacerbated inflammation in these conditions. The loss of oxytocin’s ability to suppress pro-inflammatory cytokines such as TNF-α, IL-1β, and IL-6 results in prolonged immune activation, contributing to disease progression and tissue damage [48].
Neurodegenerative diseases: AD and Parkinson’s disease are examples of neurodegenerative conditions, where chronic neuroinflammation plays a key role in disease pathology. Oxytocin’s neuroprotective and anti-inflammatory properties, suggest that dysregulated oxytocin levels may contribute to the neuro-inflammatory processes observed in these diseases. Impaired oxytocin signalling may exacerbate microglial activation, leading to chronic inflammation in the brain, which accelerates neurodegeneration. Immune deficiency and infections: Oxytocin is also involved in immune responses to infections. In cases of immune deficiency, such as HIV/AIDS or primary immunodeficiencies, altered oxytocin signalling may exacerbate immune dysfunction. The lack of oxytocin’s immunomodulatory effects could result in a weakened immune response, increasing susceptibility to infections and impairing the body’s ability to mount an effective defence against pathogens. Furthermore, impaired oxytocin production can hinder the resolution of inflammation, leading to chronic, low-grade inflammation, which is detrimental in immune-deficient states [5].
Psychoneuroimmunological disorders: Disorders that involve the interplay between psychological stress and immune dysfunction, such as chronic fatigue syndrome (CFS) and fibromyalgia, may also involve dysregulated oxytocin signalling. In these conditions, chronic stress and heightened inflammatory responses are common, and oxytocin’s potential to modulate both stress and immune function suggests it may be an important factor in disease pathogenesis. Oxytocin dysregulation in these disorders could contribute to the maintenance of inflammatory processes, muscle pain, and fatigue, hallmark features of CFS, and fibromyalgia [49]

7. Conclusion
The relationship between oxytocin and the immune system is an area of growing scientific interest, revealing intricate connections between this well-known neuropeptide and immune function. Oxytocin’s ability to modulate immune responses, influence inflammatory pathways, and regulate immune cell activity suggests that it plays a central role in maintaining immune homeostasis. This conclusion summarizes the key findings of the review, discusses the implications for future research, and offers final remarks on the potential of oxytocin in immune system regulation and therapeutic applications.

7.1. Summary of key findings
This review highlighted several important aspects of the interactions between oxytocin and the immune system:
Oxytocin’s impact on immune modulation: Oxytocin influences a variety of immune processes, including the regulation of cytokine production, immune cell activation, and the balance between pro-inflammatory and anti-inflammatory responses. By modulating these processes, oxytocin helps maintain immune homeostasis and prevent excessive inflammation.
Molecular and genetic mechanisms: The role of oxytocin in immune function is mediated through its receptors (OXTRs), signalling pathways such as NF-κB and MAPK, and genetic regulation of its synthesis and release. Alterations in oxytocin receptor function or signalling pathways can disrupt immune regulation and contribute to various inflammatory and autoimmune diseases.
Oxytocin and inflammatory response: Oxytocin plays a critical role in controlling inflammatory pathways, inhibiting excessive cytokine release, and promoting immune tolerance. The peptide’s ability to modulate oxidative stress and the inflammatory response positions it as a potential therapeutic agent for inflammatory diseases and conditions marked by chronic inflammation.
Oxytocin and immune dysfunction: Dysregulation of oxytocin signalling is implicated in immune dysfunction, contributing to autoimmune diseases, chronic inflammatory conditions, and immune deficiencies. A lack of oxytocin or impaired receptor function can lead to immune imbalance, resulting in heightened inflammation or compromised immune responses.
Therapeutic potential: The review discussed the potential for oxytocin-based therapies to restore immune balance in various conditions, such as autoimmune diseases, neuroinflammation, chronic inflammation, and immune deficiencies. Oxytocin’s ability to reduce inflammation, modulate immune cell activity, and alleviate stress-induced immune dysfunction suggests that it could be a novel therapeutic agent for immune-related disorders.

7.2. Implications for future research
Despite the promising findings, several aspects of oxytocin’s role in immune system regulation require further investigation. Future research should focus on:
Mechanistic insights: More detailed studies are needed to understand the precise molecular mechanisms through which oxytocin modulates immune function. This includes exploring the specific signalling pathways involved, the genetic regulation of oxytocin synthesis, and the downstream effects of oxytocin receptor activation in immune cells.
Clinical trials: While preclinical studies suggest the therapeutic potential of oxytocin in managing inflammation and immune dysfunction, clinical trials are necessary to validate its efficacy and safety in humans. This includes testing oxytocin or oxytocin analogues in patients with autoimmune diseases, chronic inflammation, and neurodegenerative conditions.
Oxytocin in immune deficiency: Research exploring the role of oxytocin in immune deficiencies, such as HIV/AIDS or primary immunodeficiencies, could provide valuable insights into its potential as an immune-enhancing therapeutic agent. Investigating how oxytocin may help restore immune function in these conditions could open new avenues for treatment.
Oxytocin-based therapeutics: Development of oxytocin-based therapeutic strategies, either through pharmacological administration or behavioural interventions to increase oxytocin levels (e.g. social bonding, touch therapy), should be a priority. Understanding how these approaches can modulate immune function and inflammation will be essential in harnessing the full potential of oxytocin in clinical settings.

Acknowledgements
The authors would like to thank all authors included in this systematic review.

Compliance with ethical guidelines
This article is a review with no human or animal sample.

Funding
This research did not receive any grant from funding agencies in the public, commercial, or non-profit sectors.

Authors' contributions
Conceptualization and writing: Muhammad Yasir Naeem and Zeliha Selamoglu; Data curation and investigation: Elifsena Canan Alp Arici and Shahid Abbas.

Conflict of interest
The authors declared no conflict of interests. 

​​​​​​​Data availability
The data supporting the findings of this study are available upon reasonable request from the corresponding author.

References

1. Neumann ID. Monitoring oxytocin signaling in the brain: More than a love story. Compr Psychoneuroendocrinol. 2023; 16:100206. [DOI:10.1016/j.cpnec.2023.100206] [PMID]
2. Dantzer R. Neuroimmune interactions: From the brain to the immune system and vice versa. Physiol Rev. 2018; 98(1):477-504. [DOI:10.1152/physrev.00039.2016] [PMID]
3. Carter CS. Oxytocin and love: Myths, metaphors and mysteries. Compr Psychoneuroendocrinol. 2021; 9:100107.[DOI:10.1016/j.cpnec.2021.100107] [PMID]
4. Jiang J, Yang M, Tian M, Chen Z, Xiao L, Gong Y. Intertwined associations between oxytocin, immune system and major depressive disorder. Biomed Pharmacother. 2023; 163:114852. [DOI:10.1016/j.biopha.2023.114852] [PMID]
5. Friuli M, Eramo B, Valenza M, Scuderi C, Provensi G, Romano A. Targeting the oxytocinergic system: A possible pharmacological strategy for the treatment of inflammation occurring in different chronic diseases. Int J Mol Sci. 2021; 22(19):10250. [DOI:10.3390/ijms221910250] [PMID]
6. King LB, Walum H, Inoue K, Eyrich NW, Young LJ. Variation in the oxytocin receptor gene predicts brain region-specific expression and social attachment. Biol Psychiatry. 2016; 80(2):160-9. [DOI:10.1016/j.biopsych.2015.12.008] [PMID]
7. Resurreccion EP, Fong KW. The integration of Metabolomics with other Omics: Insights into understanding prostate cancer. Metabolites. 2022; 12(6):488. [DOI:10.3390/metabo12060488] [PMID]
8. Feixiang L, Yanchen F, Xiang L, Yunke Z, Jinxin M, Jianru W, et al. The mechanism of oxytocin and its receptors in regulating cells in bone metabolism. Front Pharmacol. 2023; 14:1171732. [DOI:10.3389/fphar.2023.1171732] [PMID]
9. Zaidi M, Yuen T, Kim SM. Pituitary crosstalk with bone, adipose tissue and brain. Nat Rev Endocrinol. 2023; 19(12):708-21. [DOI:10.1038/s41574-023-00894-5] [PMID]
10. Tian YQ, Liu J, Cheng P, Zou J, Xu HF, Shi XH, et al. Dual COX-2/5-LOX inhibitors from Zanthoxylum simulans inhibit gastric cancer cells by cross-mediating thyroid, estrogen, and oxytocin signaling pathways. Front Chem. 2024; 11:1287570. [DOI:10.3389/fchem.2023.1287570] [PMID]
11. Malik M. The effect of oxytocin receptor genetic variants on oxytocin response [PhD dissertation]. St. Louis: Washington University in St. Louis ; 2023. [Link]
12. Danoff JS, Page EA, Perkeybile AM, Kenkel WM, Yee JR, Ferris CF, et al. Transcriptional diversity of the oxytocin receptor in prairie voles: mechanistic implications for behavioral neuroscience and maternal physiology. Front Genet. 2023; 14:1225197. [DOI:10.3389/fgene.2023.1225197] [PMID]
13. Hasan R. The multifaceted role of oxytocinergic system and OXTR gene. Glob Med Genet. 2024; 11(01):29-33. [DOI:10.1055/s-0044-1779039] [PMID]
14. Nance MG, Sullivan KM, Puglia MH. The impact of the early environment on oxytocin receptor epigenetics and potential therapeutic implications. Pediatr Res. 2025; 97(4):1290-304. [DOI:10.1038/s41390-024-03563-z] [PMID]
15. MacLean EL, Carranza E, Gnanadesikan GE, King KM, Allen AM, Linde-Krieger LB, et al. Neurophysin I is an analytically robust surrogate biomarker for oxytocin. Psychoneuroendocrinology. 2024; 161:106951. [DOI:10.1016/j.psyneuen.2023.106951] [PMID]
16. Jin Y, Song D, Yan Y, Quan Z, Qing H. The role of oxytocin in early-life-stress-related neuropsychiatric disorders. Int J Mol Sci. 2023; 24(13):10430. [DOI:10.3390/ijms241310430] [PMID]
17. Mehdi SF, Pusapati S, Khenhrani RR, Farooqi MS, Sarwar S, Alnasarat A, et al. Oxytocin and related peptide hormones: Candidate anti-inflammatory therapy in early stages of sepsis. Front Immunol. 2022; 13:864007. [DOI:10.3389/fimmu.2022.864007] [PMID]
18. Lee C, Lee H, Park JC, Im SH. Microbial components and effector molecules in T helper cell differentiation and function. Immune Netw. 2023; 23(1):e7. [DOI:10.4110/in.2023.23.e7] [PMID]
19. Imami AS, O’Donovan SM, Creeden JF, Wu X, Eby H, McCullumsmith CB, et al. Oxytocin’s anti-inflammatory and proimmune functions in COVID-19: A transcriptomic signature-based approach. Physiol Genomics. 2020; 52(9):401-7.[DOI:10.1152/physiolgenomics.00095.2020] [PMID]
20. Simons RL, Lei MK, Beach SRH, Cutrona CE, Philibert RA. Methylation of the oxytocin receptor gene mediates the effect of adversity on negative schemas and depression. Dev Psychopathol. 2017; 29(3):725-36. [DOI:10.1017/S0954579416000420] [PMID]
21. Jiang ST, Lian SY, Sun YH, Pan MB, Wang B, Wang H, et al. The oxytocin receptor is essential for the protective effect of pair housing on post-stroke depression in mice. Exp Gerontol. 2024; 190:112432. [DOI:10.1016/j.exger.2024.112432] [PMID]
22. Danoff JS, Wroblewski KL, Graves AJ, Quinn GC, Perkeybile AM, Kenkel WM, et al. Genetic, epigenetic, and environmental factors controlling oxytocin receptor gene expression. Clin Epigenetics. 2021; 13(1):23. [DOI:10.1186/s13148-021-01017-5] [PMID]
23. Gryksa K, Neumann ID. Consequences of pandemic-associated social restrictions: Role of social support and the oxytocin system. Psychoneuroendocrinology. 2022; 135:105601. [DOI:10.1016/j.psyneuen.2021.105601] [PMID]
24. Gardashli M, Baron M, Drohat P, Quintero D, Kaplan LD, Szeto A, et al. The roles of regulatory-compliant media and inflammatory/oxytocin priming selection in enhancing human mesenchymal stem/stromal cell immunomodulatory properties. Sci Rep. 2024; 14(1):29438. [DOI:10.1038/s41598-024-80050-9] [PMID]
25. Karagiannis P, Correa I, Chauhan J, Cheung A, Dominguez-Rodriguez D, Terranova-Barberio M, et al. Innate stimulation of B cells ex vivo enhances antibody secretion and identifies tumour-reactive antibodies from cancer patients. Clin Exp Immunol. 2022; 207(1):84-94. [DOI:10.1093/cei/uxab005] [PMID]
26. Buemann B, Uvnäs-Moberg K. Oxytocin may have a therapeutical potential against cardiovascular disease. Possible pharmaceutical and behavioral approaches. Med Hypotheses. 2020; 138:109597. [DOI:10.1016/j.mehy.2020.109597] [PMID]
27. Lawrence T. The nuclear factor NF-κB pathway in inflammation. Cold Spring Harb Perspect Biol. 2009; 1(6):a001651. [DOI:10.1101/cshperspect.a001651] [PMID]
28. Takayanagi Y, Onaka T. Roles of oxytocin in stress responses, allostasis and resilience. Int J Mol Sci. 2021; 23(1):150. [DOI:10.3390/ijms23010150] [PMID]
29. Turner MD, Nedjai B, Hurst T, Pennington DJ. Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease. Biochim Biophys Acta. 2014; 1843(11):2563-82. [DOI:10.1016/j.bbamcr.2014.05.014] [PMID]
30. Sokol CL, Luster AD. The chemokine system in innate immunity. Cold Spring Harb Perspect Biol. 2015; 7(5):a016303.[DOI:10.1101/cshperspect.a016303] [PMID]
31. Abdul-Rahman T, Ghosh S, Badar SM, Nazir A, Bamigbade GB, Aji N, et al. The paradoxical role of cytokines and chemokines at the tumor microenvironment: A comprehensive review. Eur J Med Res. 2024; 29(1):124. [DOI:10.1186/s40001-024-01711-z] [PMID]
32. Berger A. Th1 and Th2 responses: What are they? BMJ. 2000; 321(7258):424. [DOI:10.1136/bmj.321.7258.424] [PMID]
33. Calvillo-Robledo A, Ramírez-Farías C, Valdez-Urias F, Huerta-Carreón EP, Quintanar-Stephano A. Arginine vasopressin hormone receptor antagonists in experimental autoimmune encephalomyelitis rodent models: A new approach for human multiple sclerosis treatment. Front Neurosci. 2023; 17:1138627. [DOI:10.3389/fnins.2023.1138627] [PMID]
34. Mehdi SF, Pusapati S, Anwar MS, Lohana D, Kumar P, Nandula SA, et al. Glucagon-like peptide-1: A multi-faceted anti-inflammatory agent. Front Immunol. 2023; 14:1148209. [DOI:10.3389/fimmu.2023.1148209] [PMID]
35. Davis LS, Hutcheson J, Mohan C. The role of cytokines in the pathogenesis and treatment of systemic lupus erythematosus. J Interferon Cytokine Res. 2011; 31(10):781-9. [DOI:10.1089/jir.2011.0047] [PMID]
36. Bell AF, Erickson EN, Carter CS. Beyond labor: The role of natural and synthetic oxytocin in the transition to motherhood. J Midwifery Womens Health. 2014; 59(1):35-42. [DOI:10.1111/jmwh.12101] [PMID]
37. Chen L, Deng H, Cui H, Fang J, Zuo Z, Deng J, et al. Inflammatory responses and inflammation-associated diseases in organs. Oncotarget. 2017; 9(6):7204-18. [DOI:10.18632/oncotarget.23208] [PMID]
38. Liu T, Zhang L, Joo D, Sun SC. NF-κB signaling in inflammation. Signal Transduct Target Ther. 2017; 2:17023. [DOI:10.1038/sigtrans.2017.23] [PMID]
39. Stevenson JR, McMahon EK, McNeely TL, Haussmann MF. Oxytocin prevents dysregulation of the acute stress response and glucocorticoid-induced oxidative stress in chronically isolated prairie voles. Psychoneuroendocrinology. 2023; 153:106121. [DOI:10.1016/j.psyneuen.2023.106121] [PMID]
40. Inoue T, Yamakage H, Tanaka M, Kusakabe T, Shimatsu A, Satoh-Asahara N. Oxytocin suppresses inflammatory responses induced by lipopolysaccharide through inhibition of the eIF-2α-ATF4 pathway in mouse microglia. Cells. 2019; 8(6):527. [DOI:10.3390/cells8060527] [PMID]
41. Marín-Prida J, Rodríguez-Ulloa A, Besada V, Llopiz-Arzuaga A, Batista NV, Hernández-González I, et al. The effects of Phycocyanobilin on experimental arthritis involve the reduction in nociception and synovial neutrophil infiltration, inhibition of cytokine production, and modulation of the neuronal proteome. Front Immunol. 2023; 14:1227268. [DOI:10.3389/fimmu.2023.1227268] [PMID]
42. Welch MG, Anwar M, Chang CY, Gross KJ, Ruggiero DA, Tamir H, et al. Combined administration of secretin and oxytocin inhibits chronic colitis and associated activation of forebrain neurons. Neurogastroenterol Motil. 2010; 22(6):654-e202. [DOI:10.1111/j.1365-2982.2010.01477.x] [PMID]
43. Rusch JA, Layden BT, Dugas LR. Signalling cognition: The gut microbiota and hypothalamic-pituitary-adrenal axis. Front Endocrinol (Lausanne). 2023; 14:1130689. [DOI:10.3389/fendo.2023.1130689] [PMID]
44. Franco JH, Chen X, Pan ZK. Novel treatments targeting the dysregulated cell signaling pathway during sepsis. J Cell Signal. 2021; 2(4):228-34. [DOI:10.33696/Signaling.2.055]
45. Wang SC, Zhang F, Zhu H, Yang H, Liu Y, Wang P, et al. Potential of endogenous oxytocin in endocrine treatment and prevention of COVID-19. Front Endocrinol. 2022; 13:799521. [DOI:10.3389/fendo.2022.799521] [PMID]
46. Selles MC, Fortuna JTS, de Faria YPR, Siqueira LD, Lima-Filho R, Longo BM, et al. Oxytocin attenuates microglial activation and restores social and non-social memory in APP/PS1 Alzheimer model mice. iScience. 2023; 26(4):106545. [DOI:10.1016/j.isci.2023.106545] [PMID]
47. El-Ganainy SO, Soliman OA, Ghazy AA, Allam M, Elbahnasi AI, Mansour AM, et al. Intranasal oxytocin attenuates cognitive impairment, β-amyloid burden and tau deposition in female rats with Alzheimer’s disease: Interplay of ERK1/2/GSK3β/caspase-3. Neurochem Res. 2022; 47(8):2345-56. [DOI:10.1007/s11064-022-03624-x] [PMID]
48. Espinosa De Los Monteros-Zúñiga A, Martínez-Lorenzana G, Condés-Lara M, González-Hernández A. Intrathecal oxytocin improves spontaneous behavior and reduces mechanical hypersensitivity in a rat model of postoperative pain. Front Pharmacol. 2020; 11:581544. [DOI:10.3389/fphar.2020.581544] [PMID]
49. Szeto A, Rossetti MA, Mendez AJ, Noller CM, Herderick EE, Gonzales JA, et al. Oxytocin administration attenuates atherosclerosis and inflammation in Watanabe Heritable Hyperlipidemic rabbits. Psychoneuroendocrinology. 2013; 38(5):685-93 [DOI:10.1016/j.psyneuen.2012.08.009] [PMID]