Oxytocin and Related Peptide Hormones: Candidate Anti-Inflammatory Therapy in Early Stages of Sepsis

Abstract

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-hospitalization and recovery may be incomplete, with long term sequelae including post-sepsis syndrome. Consequently, sepsis continues to be a leading cause of morbidity and mortality across the world. In our recent review of human chorionic gonadotropin (hCG), we noted that its major properties including promotion of fertility, parturition, and lactation were described over a century ago. By contrast, the anti-inflammatory properties of this hormone have been recognized only more recently. Vasopressin, a hormone best known for its anti-diuretic effect, also has anti-inflammatory actions. Surprisingly, vasopressin’s close cousin, oxytocin, has broader and more potent anti-inflammatory effects than vasopressin and a larger number of pre-clinical studies supporting its potential role in limiting sepsis-associated organ damage. This review explores possible links between oxytocin and related octapeptide hormones and sepsis-related modulation of pro-inflammatory and anti-inflammatory activities.

Oxytocin alleviates periodontitis in adult rats

“…Thus, it has been reported that OXT blocks the activation of inflammatory cells of the immune system, decreases cytokine levels and microglial activation in the central nervous system, decreases ischemia-reperfusion inflammation in the cardiovascular and musculoskeletal systems, lowers inflammatory cytokines in the gastrointestinal system, protects against LPSinduced acute lung injury, and decrease inflammation in adipocytes and in pyelonephritis. 11,14,[29][30][31] We have also demonstrated that OXT prevents alveolar bone loss. Our result is consistent with the findings that the stimulation of OXTR present in osteoclasts results in an inhibited bone resorption, 32 suggesting that OXT contributes to bone protection and/or regeneration in gingival tissues.…”

“…[10][11][12] It has been reported the anti-inflammatory effects of OXT in the cardiovascular, gastrointestinal, endocrine, genitourinary, and central nervous systems. 11 OXT acts via its receptor (OXTR), which belongs to the heptahelical G protein-coupled receptor family, that has been detected in a broad diversity of cells and particularly in immune cells like neutrophils, macrophages, and lymphocytes. 10,13 Thus, OXT reduces expression levels of proinflammatory mediators and cytokines in cultured macrophages and endothelial cells 14 and attenuates the overactivation of microglial cells in vitro.…”

“…Oxytocin (OXT) is a nonapeptide mainly produced in the paraventricular and the supraoptic nuclei in the hypothalamus with several functions in the periphery. Besides its role in lactation and parturition, OXT has been suggested to participate in the modulation of immune and inflammatory processes 10–12 . It has been reported the anti‐inflammatory effects of OXT in the cardiovascular, gastrointestinal, endocrine, genitourinary, and central nervous systems 11 .…”

Intertwined associations between oxytocin, immune system and major depressive disorder

“…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.…”

Oxytocin: A Multi-Functional Biomolecule with Potential Actions in Dysfunctional Conditions; From Animal Studies and Beyond

“…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 [ 210 ] 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 [ 211 ].…”