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The immune and nervous systems are closely interrelated through their messenger molecules: cytokines, hormones and nitric oxide. There are sex differences in the magnitude of the inflammatory response and one of the mechanism by which female sex steroids modulate the inflammatory response could be through the hypothalamo-pituitary-adrenal axe(HPA axes). In this study, we aimed to investigate the inter-relationship between the different levels of estradiol hormone and the different inflammatory stimuli on the HPA axis response, and the role of interleukin 6(IL6) and nitric oxide (NO). This was achieved by using 100 female albino rats divided in to 3 main groups: The first group was the sham group, which was used to test the effect of all sham procedures used in the study. The two other groups represented the two inflammatory states: local (induced by formaline injection) and systemic (cecal ligation and puncture: CLP). Under each inflammatory state, the effect of intact ovary, estradiol treated ovariectomy and placebo treated ovariectomy were studied. HPA responses were evaluated, 24 hours after the sham or the inflammatory procedure, through the measurement of the plasma levels of Corticotropin-releasing Hormone (CRH), adrenocorticotropes Hormone (ACTH) and cortisol. Both IL6 and nitrite were also measured.We found that high physiological levels of estradiol reduced the enhanced HPA response induced by different inflammatory mediators during systemic and local inflammation. With significant enhancement of the HPA response observed mainly during local inflammation. We conclude that both the levels of estradiol hormone and the type of inflammation seem to play an important determining role on HPA response. IL6 and NO play important roles that could explain the previous findings.

Evaluation of the effects of estradiol on the hypothalamic-pitutary adrenal axis response during systemic and local inflammation