Iwasa T, Matsuzaki T, Gereltsetseg G, Munkhzaya M, Tungalagsurv A, Murakami M, Yamasaki M, Yamamoto Y, Kuwahara A, Kato T, Yasui T, Irahara M
Department of Obstetrics and Gynecology, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-15 Kuramoto-Cho, Tokushima, 770-8503, Japan.
J Endocrinol Invest. 2014 Aug;37(8):721-727. doi: 10.1007/s40618-014-0094-5. Epub 2014 Jun 13.
The immune response is altered according to hormonal and metabolic status. Obesity increases the inflammatory and fever response, whereas loss of gonadal steroid decreases behavioral response to immune stress. However, the immune systems of ovariectomized animals exhibiting obesity and gonadal steroid deficiency, particularly under septic conditions, have not been fully examined. In the present study, we evaluated the ovariectomy-induced changes of central and peripheral immune responses to life-threatening septic stimulus.
Ovariectomized rats showed heavier body weight and lighter uterine weight when compared with gonadally intact rats. Fever response to septic dose of lipopolysaccharide (LPS) in ovariectomized rats was less evident when compared with that in gonadally intact rats. In addition, under LPS-injected septic conditions, hypothalamic gene levels of Interleukin-1β (IL-1β), Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) and serum protein levels of IL-1β and TNF-α in ovariectomized rats were lower than those in gonadally intact rats. On the other hand, IL-6 levels in visceral fat under septic conditions were higher in ovariectomized rats than in gonadally intact rats.
These findings indicate that ovariectomy-induced site-specific changes in cytokine response under septic conditions. As hypothalamic, but not peripheral, pro-inflammatory cytokines are directly involved in the fever response, the attenuation of fever response observed in ovariectomized rats may be caused by a reduction in central cytokine responses.
免疫反应会根据激素和代谢状态而改变。肥胖会增强炎症和发热反应，而性腺类固醇的缺失会降低对免疫应激的行为反应。然而，对于表现出肥胖和性腺类固醇缺乏的去卵巢动物的免疫系统，尤其是在脓毒症条件下，尚未进行充分研究。在本研究中，我们评估了去卵巢诱导的对危及生命的脓毒症刺激的中枢和外周免疫反应的变化。
与性腺完整的大鼠相比，去卵巢大鼠体重更重，子宫重量更轻。与性腺完整的大鼠相比，去卵巢大鼠对脓毒症剂量的脂多糖（LPS）的发热反应不那么明显。此外，在注射LPS的脓毒症条件下，去卵巢大鼠下丘脑白细胞介素-1β（IL-1β）、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）的基因水平以及血清中IL-1β和TNF-α的蛋白水平均低于性腺完整的大鼠。另一方面，在脓毒症条件下，去卵巢大鼠内脏脂肪中的IL-6水平高于性腺完整的大鼠。
这些发现表明去卵巢在脓毒症条件下诱导了细胞因子反应的位点特异性变化。由于下丘脑而非外周的促炎细胞因子直接参与发热反应，去卵巢大鼠中观察到的发热反应减弱可能是由中枢细胞因子反应的降低所致。
