Mouihate A, Pittman Q J
Neuroscience Research Group, Department of Physiology and Biophysics, Faculty of Medicine, University of Calgary, Alberta, Canada T2N 4N1.
Endocrinology. 2003 Jun;144(6):2454-60. doi: 10.1210/en.2002-0093.
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-1beta. 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-1beta was potentiated by the ovarian hormone replacement. IL-1beta 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-1beta production and COX-2 expression in the hypothalamus. The markedly different action of ovarian hormones on IL-1beta 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-1beta.
本研究的目的是探讨卵巢激素是否以及如何与对热原的发热反应相互作用。与卵巢切除的对照组相比，对卵巢切除的大鼠进行雌激素和孕激素治疗与脂多糖（LPS）诱导的发热减少有关。LPS发热的减少伴随着下丘脑诱导型环氧化酶-2（COX-2）蛋白表达水平的降低以及血浆中IL-1β水平的降低。血浆中LPS诱导的IL-6量不受卵巢激素替代的影响。相反，卵巢激素替代增强了对腹腔注射IL-1β的下丘脑COX-2表达。IL-1β诱导血浆中IL-6水平适度升高，而卵巢激素替代可抑制这种升高。这些数据表明，卵巢激素替代通过抑制LPS诱导的下丘脑IL-1β产生和COX-2表达，减弱了对LPS的促炎反应。卵巢激素对IL-1β和LPS作用的显著不同表明，这种性激素对免疫反应的调节是感染性质的一种功能，并进一步证明LPS的作用不同于IL-1β的作用。
