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Neuroimmune Response to Endogenous and Exogenous Pyrogens Is Differently Modulated by Sex Steroids

Neuroscience Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Alberta, Canada T2N 4N1

Address all correspondence and requests for reprints to: Abdeslam Mouihate, Ph.D., Neuroscience Research Group, Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1. E-mail: mouihate{at}ucalgary.ca.

The objective of this study was to explore whether and how ovarian hormones interact with the febrile response to pyrogens. Estrogen and progesterone treatment of ovariectomized rats was associated with a reduction in lipopolysaccharide (LPS)-induced fever, compared with ovariectomized controls. LPS-fever reduction was accompanied by reduced levels of the inducible cyclooxygenase-2 (COX-2) protein expression in the hypothalamus as well as reduced plasma levels of IL-1ß. The amount of LPS-induced IL-6 in the plasma was not affected by ovarian hormone replacement. In contrast, hypothalamic COX-2 expression in response to intraperitoneal injection of IL-1ß was potentiated by the ovarian hormone replacement. IL-1ß induced a moderate increase in plasma levels of IL-6 that was suppressed by ovarian hormone replacement. These data suggest that ovarian hormone replacement attenuated the proinflammatory response to LPS by suppressing the LPS-induced IL-1ß production and COX-2 expression in the hypothalamus. The markedly different action of ovarian hormones on IL-1ß and LPS effects suggests that this sex hormone modulation of the immune response is a function of the nature of infection and provides further evidence that LPS actions are different from those of IL-1ß.

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