ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2008) 16 OC1.9

Oxytocin alleviates the neuroendocrine and cytokine response to bacterial endotoxin in healthy men

Greisa Vila1, Martin Clodi1, René Geyeregger1, Michaela Riedl1, Thomas M Stulnig1, Joachim Struck2, Thomas A Luger3 & Anton Luger1

1Division of Endocrinology and Metabolism, Department of Internal Medicine III, Medical University of Vienna, Vienna, Austria; 2Research Department, BRAHMS AG, Biotechnology Centre, Hennigsdorf, Germany; 3Department of Dermatology, University Hospital Münster, Münster, Germany.

Oxytocin is a hormone and neurotransmitter with antiinflammatory and neuroimmune-modulatory properties. Physiological states of elevated plasma oxytocin levels are associated with reduced hypothalamic–pituitaty–adrenal response to different stressors. We examined the effect of exogenous oxytocin administration on bacterial endotoxin induced innate immune responses in humans. Ten healthy men received in a randomized, placebo-controlled, cross-over design (1) placebo, (2) oxytocin (1 pmol/kg per min i.v. for 90 min), (3) LPS (2 ng/kg i.v.) and (4) LPS+oxytocin. Oxytocin administration resulted in a significant transient suppression of the LPS-induced release of ACTH, cortisol, TNF-alpha, IL-1ra, MIP-1alpha, MIP-1 beta and IP-10 after endotoxin challenge in healthy volunteers. The increases of plasma procalcitonin (diagnostic and prognostic marker in sepsis), IL-4, IL-6, MCP-1 and VEGF were abolished throughout the study. In vitro, oxytocin (at concentrations of 10 pM–100 nM) had no impact on the effect of LPS in releasing TNF-alpha, IL-6 and MCP-1 in monocytes and primary blood mononuclear cells from healthy human donors. In summary, oxytocin decreases the neuroendocrine and cytokine activation caused by bacterial endotoxin in men. We exclude a direct action of oxytocin in peripheral monocytes and T lymphocytes and discuss the possibility of a pharmacological modulation of the cholinergic antiinflammatory pathway. Further studies are needed to establish a potential role of oxytocin in the therapy of inflammatory diseases, sepsis and malignancies associated with high VEGF levels.

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