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Immune functions of oxytocin. Oxytocin acts peripherally on immune cells, immune organs (thymus, spleen, bone marrow), and centrally on the nervous system to modulate its immunogenic effects. ACTH, adrenocorticotropic hormone; HSCs, hematopoietic stem cells; Ig, Immunoglobulin; IL, interleukin; MPO, myeloperoxidase; PPAR-γ, peroxisome proliferator-activated receptor gamma; PVN, paraventricular nucleus; SON, supraoptic nucleus; TSH, thyroid-stimulating hormone. Other annotations are the same as Figure 1 [Figure originates and adapted from articles (57–59)]. Up arrow (↑) symbol indicates increase, whereas down (↓) arrow symbol indicates decrease in the effect mentioned.
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Sepsis is a potentially life-threatening systemic inflammatory syndrome characterized by dysregulated host immunological responses to infection. Uncontrolled immune cell activation and exponential elevation in circulating cytokines can lead to sepsis, septic shock, multiple organ dysfunction syndrome, and death. Sepsis is associated with high re-ho...
Citations
... Sepsis is a latently life-threatening systemic inflammatory syndrome characterized by inflammatory disorders, coagulation dysfunction, and multiple organ failure. 1 World Health Organization (WHO) has emphasized the importance of sepsis because of its enormous impact on global mortality. 2 In the context of antibiotic use, the mortality rate of severe sepsis is as high as 20-30%. ...
Background: Acute lung injury (ALI) causes severe and uncontrolled pulmonary inflammation and has high morbidity in dying patients. Objective: This study aimed to evaluate the potential function of Kaempferitrin (Kae) and uncover its mechanisms in ALI. Material and Methods: We evaluated the role of Kae in ALI through the lipopolysaccharide (LPS)-induced histopathological changes, lung wet/dry (W/D) ratio, total bronchoalveolar lavage fluid (BALF) cells count, pulmonary inflammation, and the levels of interleukin (IL)-6, tumor necrosis factor-α (TNF-α), and IL-1β. The effect of Kae on NF-κB signaling pathway was discovered through the protein expression levels of transcription factors p65, p-p65, IκBα, and p-IκBα by Western blot analysis. Results: The results showed that Kae could improve lung injury by reducing apoptosis, histopathological changes, and lung W/D ratio; more importantly, Kae enhanced the survival of ALI mice. Moreover, Kae relieved inflammation, as it reduced total BALF cells count, and deceased the levels of TNF-α, IL-6, and IL-1β in serum. In addition, Western blot analysis data suggested that Kae could decrease the protein expression levels of transcription factors p65, p-p65, IκB-α, and p-IκB-α, which were promoted by LPS. Conclusion: The results of this study suggested that Kae could relieve LPS-induced ALI in mice and reduce inflammation and apoptosis through NF-κB pathway.
... Oxytocin treatment reduces inflammation and the severity of various diseases. OXTRs have been found on immune cells, including neutrophils, macrophages, and lymphocytes [47]. During inflammation, nuclear factor kappa-light-chain-enhancer (NF-κB) mediates increased OXTR expression in macrophages [48]. ...
... During inflammation, nuclear factor kappa-light-chain-enhancer (NF-κB) mediates increased OXTR expression in macrophages [48]. Oxytocin can inhibit the macrophage transition to active inflammatory cells by promoting the expression of β-arrestin 2 [47] and peroxisome proliferator-activated receptor gamma [49,50]. ...
Early-life stress during critical periods of brain development can have long-term effects on physical and mental health. Oxytocin is a critical social regulator and anti-inflammatory hormone that modulates stress-related functions and social behaviors and alleviates diseases. Oxytocin-related neural systems show high plasticity in early postpartum and adolescent periods. Early-life stress can influence the oxytocin system long term by altering the expression and signaling of oxytocin receptors. Deficits in social behavior, emotional control, and stress responses may result, thus increasing the risk of anxiety, depression, and other stress-related neuropsychiatric diseases. Oxytocin is regarded as an important target for the treatment of stress-related neuropsychiatric disorders. Here, we describe the history of oxytocin and its role in neural circuits and related behaviors. We then review abnormalities in the oxytocin system in early-life stress and the functions of oxytocin in treating stress-related neuropsychiatric disorders.
... Our recent studies have revealed the antiinflammatory properties of several peptide hormones such as hCG, oxytocin, ghrelin, and vasopressin. (3)(4)(5)(6) In this review article, we focus on the anti-inflammatory properties of the incretin hormone 'Glucagon-like Peptide-1 (GLP-1). Known for promoting glucose homeostasis and weight loss, the anti-inflammatory properties of GLP-1 suggest that it may also blunt inflammation and protect against organ damage (3)(4)(5)(6). ...
... (3)(4)(5)(6) In this review article, we focus on the anti-inflammatory properties of the incretin hormone 'Glucagon-like Peptide-1 (GLP-1). Known for promoting glucose homeostasis and weight loss, the anti-inflammatory properties of GLP-1 suggest that it may also blunt inflammation and protect against organ damage (3)(4)(5)(6). ...
... It continues to be a major cause of illness, disability, and death at all ages (211). Hormones in the body, such as oxytocin ghrelin, alpha MSH, ACTH and hCG, have a significant role in reducing the inflammatory response that occurs during sepsis (3)(4)(5)(6). GLP-1 plays a crucial role in regulating the cytokine storm by binding to receptors in a wide variety of tissues including the brain, kidneys, liver, and lungs. It reduces proinflammatory processes and boosts anti-inflammatory ones throughout the body. ...
Inflammation contributes to many chronic conditions. It is often associated with circulating pro-inflammatory cytokines and immune cells. GLP-1 levels correlate with disease severity. They are often elevated and can serve as markers of inflammation. Previous studies have shown that oxytocin, hCG, ghrelin, alpha-MSH and ACTH have receptor-mediated anti-inflammatory properties that can rescue cells from damage and death. These peptides have been studied well in the past century. In contrast, GLP-1 and its anti-inflammatory properties have been recognized only recently. GLP-1 has been proven to be a useful adjuvant therapy in type-2 diabetes mellitus, metabolic syndrome, and hyperglycemia. It also lowers HbA1C and protects cells of the cardiovascular and nervous systems by reducing inflammation and apoptosis. In this review we have explored the link between GLP-1, inflammation, and sepsis.
... Evidence suggests that certain anti-inflammatory drugs have anti-depressive effects [122]. Multiple studies have demonstrated significant anti-inflammatory effects of OXT in various diseases and systems, including the central nervous system, cardiovascular, lung, intestine, and urinary [160,161]. Oxytocin receptor (OXTR) is widely expressed in the hypothalamus, pituitary gland, adrenal gland [40], as well as in a variety of immune elements such as microglia, astrocytes, and thymus [9], all of which are affected in MDD. OXT can activate OXTR expressed on the HPA axis to suppress the abnormal immune response associated with MDD [162][163][164]. ...
Major depressive disorder (MDD) is a prominent psychiatric disorder with a high prevalence rate. The recent COVID-19 pandemic has exacerbated the already high prevalence of MDD. Unfortunately, a significant proportion of patients are unresponsive to conventional treatments, necessitating the exploration of novel therapeutic strategies. Oxytocin, an endogenous neuropeptide, has emerged as a promising candidate with anxiolytic and antidepressant properties. Oxytocin has been shown to alleviate emotional disorders by modulating the hypothalamic-pituitary-adrenal (HPA) axis and the central immune system. The dysfunction of the immune system has been strongly linked to the onset and progression of depression. The central immune system is believed to be a key target of oxytocin in ameliorating emotional disorders. In this review, we examine the evidence regarding the interactions between oxytocin, the immune system, and depressive disorder. Moreover, we summarize and speculate on the potential roles of the intertwined association between oxytocin and the central immune system in treating emotional disorders.
... From the previously mentioned research, is it evident that although there is a potential for the use of oxytocin into COVID-19 patients, animal studies are needed to explore oxytocin treatment on these patients. In an earlier study in mice [170] (Table 1) and in other studies presented in a review on the treatment of sepsis, among other diseases [211] OXT and related peptides might have a therapeutic role. Signs of multi-organ injury typical of sepsis occur in approximately 2-5% of COVID-19 patients 8-10 days post-infection, hence OXT potentially could alleviate this complication [212]. ...
Oxytocin is a hormone secreted from definite neuroendocrine neurons located in specific nuclei in the hypothalamus (mainly from paraventricular and supraoptic nuclei), and its main known function is the contraction of uterine and/or mammary gland cells responsible for parturition and breastfeeding. Among the actions of the peripherally secreted oxytocin is the prevention of different degenerative disorders. These actions have been proven in cell culture and in animal models or have been tested in humans based on hypotheses from previous studies. This review presents the knowledge gained from the previous studies, displays the results from oxytocin intervention and/or treatment and proposes that the well described actions of oxytocin might be connected to other numerous, diverse actions of the biomolecule.
Objective
The objective of the study was to evaluate the expression of oxytocin receptors in normal and inflamed gingiva, as well as the effects of systemic administration of oxytocin in bone loss and gum inflammatory mediators in a rat model of experimental periodontitis.
Background Data
Current evidence supports the hypothesis of a disbalance between the oral microbiota and the host's immune response in the pathogenesis of periodontitis. Increased complexity of the microbial biofilm present in the periodontal pocket leads to local production of nitrogen and oxygen‐reactive species, cytokines, chemokines, and other proinflammatory mediators which contribute to periodontal tissue destruction and bone loss. Oxytocin has been suggested to participate in the modulation of immune and inflammatory processes. We have previously shown that oxytocin, nitric oxide, and endocannabinoid system interact providing a mechanism of regulation for systemic inflammation. Here, we aimed at investigating not only the presence and levels of expression of oxytocin receptors on healthy and inflamed gingiva, but also the effects of oxytocin treatment on alveolar bone loss, and systemic and gum expression of inflammatory mediators involved in periodontal tissue damage using ligature‐induced periodontitis. Therefore, anti‐inflammatory strategies oriented at modulating the host's immune response could be valuable adjuvants to the main treatment of periodontal disease.
Methods
We used an animal model of ligature‐induced periodontitis involving the placement of a linen thread (Barbour flax 100% linen suture, No. 50; size 2/0) ligature around the neck of first lower molars of adult male rats. The ligature was left in place during the entire experiment (7 days) until euthanasia. Animals with periodontitis received daily treatment with oxytocin (OXT, 1000 μg/kg, sc.) or vehicle and/or atosiban (3 mg/kg, sc.), an antagonist of oxytocin receptors. The distance between the cement–enamel junction and the alveolar bone crest was measured in stained hemimandibles in the long axis of both buccal and lingual surfaces of both inferior first molars using a caliper. TNF‐α levels in plasma were determined using specific rat enzyme‐linked immunosorbent assays (ELISA). OXT receptors, IL‐6, IL‐1β, and TNF‐α expression were determined in gingival tissues by semiquantitative or real‐time PCR.
Results
We show that oxytocin receptors are expressed in normal and inflamed gingival tissues in male rats. We also show that the systemic administration of oxytocin prevents the experimental periodontitis‐induced increased gum expression of oxytocin receptors, TNF‐α, IL‐6, and IL‐1β ( p < .05). Furthermore, we observed a reduction in bone loss in rats treated with oxytocin in our model.
Conclusions
Our results demonstrate that oxytocin is a novel and potent modulator of the gingival inflammatory process together with bone loss preventing effects in an experimental model of ligature‐induced periodontitis.
Background:
Sepsis-associated encephalopathy (SAE) is a diffuse brain dysfunction, characterized by cognitive and memory impairments closely linked to hippocampal dysfunction. Though it is well-known that SAE is a diffuse brain dysfunction with microglial activation, the pathological mechanisms of SAE are not well established and effective clinical interventions are lacking. Oxytocin (OXT) is reported to have anti-inflammatory and neuroprotective roles. However, the effects of OXT on SAE and the underlying mechanisms are not clear.
Methods:
SAE was induced in adult C57BL/6J male mice by cecal ligation and perforation (CLP) surgery. Exogenous OXT was intranasally applied after surgery. Clinical score, survivor rate, cognitive and memory behaviors, and hippocampal neuronal and non-neuronal functions were evaluated. Cultured microglia challenged with lipopolysaccharide (LPS) were used to investigate the effects of OXT on microglial functions, including inflammatory cytokines release and phagocytosis. The possible intracellular signal pathways involved in the OXT-induced neuroprotection were explored with RNA sequencing.
Results:
Hippocampal OXT level decreases, while the expression of OXT receptor (OXTR) increases around 24 h after CLP surgery. Intranasal OXT application at a proper dose increases mouse survival rate, alleviates cognitive and memory dysfunction, and restores hippocampal synaptic function and neuronal activity via OXTR in the SAE model. Intraperitoneal or local administration of the OXTR antagonist L-368,899 in hippocampal CA1 region inhibited the protective effects of OXT. Moreover, during the early stages of sepsis, hippocampal microglia are activated, while OXT application reduces microglial phagocytosis and the release of inflammatory cytokines, thereby exerting a neuroprotective effect. OXT may improve the SAE outcomes via the OXTR-ERK-STAT3 signaling pathway.
Conclusion:
Our study uncovers the dysfunction of the OXT signal in SAE and shows that intranasal OXT application at a proper dose can alleviate SAE outcomes by reducing microglial overactivation, suggests that OXT may be a promising therapeutic approach in managing SAE patients.
Background
Mesenchymal stem cells (MSCs) are capable of secreting different substances, including the anti-inflammatory protein TSG-6, which can be useful in the treatment of diseases with inflammatory reactions. The main aim of this study was to evaluate the expression of the TSG-6 gene in MSCs derived from the umbilical cord. For better understanding of the anti-inflammatory properties of MSCs, we additionally assessed the expression of some interleukins (ILs).
Material/Methods
The study group included 45 patients after delivery, aged from 21 to 46 years; the average patient age was 33 years. MSCs were isolated enzymatically from umbilical cord Wharton’s jelly, in vitro cultured, and characterized using flow cytometry; qPCR was performed to assess expression of the studied genes. The expression of genes of a number of pro-inflammatory ILs in MSCs was investigated in relation to the health of patients (coexistence of hypertension), the level of leukocytes, pCO2, and hemoglobin in the blood.
Results
Our research showed that the expression of the TSG-6 gene in MSCs depends on coexisting diseases in the patient and the biochemical parameters of umbilical cord blood, including the important role of cord blood pH. We found that the levels of IL2 and IL6 expression were correlated with pCO2, and IL6 expression were correlated with pO2.
Conclusions
Our study suggests that maternal health status and cord blood biochemical parameters could affect the anti-inflammatory properties of MSCs; however, this needs to be confirmed in a future study.
Body surfaces are colonized by an enormous array of microbes collectively referred to as the microbiota. In the past decade, there has been an increase in research activity directed toward understanding the importance of microbiota for human health and disease. This research activity has clearly established that the commensal microbiota play an essential role in the development and maintenance of physiological processes, including neuroendocrine and immune responses, throughout life. Although our understanding of exactly how these microbes exert their effects on the host is still in its infancy, multiple pathways have been identified in recent years. These pathways are described here, along with a description of some of the tools needed for their study.
