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首页> 外文期刊>Cytokine >Estrogen alters baseline and inflammatory-induced cytokine levels independent from hypothalamic-pituitary-adrenal axis activity
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Estrogen alters baseline and inflammatory-induced cytokine levels independent from hypothalamic-pituitary-adrenal axis activity

机译：雌激素改变基线和炎症诱导的细胞因子水平，独立于下丘脑-垂体-肾上腺轴活动

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Although estrogen reduces inflammatory-mediated pain responses, the mechanisms behind its effects are unclear. This study investigated if estrogen modulates inflammatory signaling by reducing baseline, or inflammation-induced cytokine levels in the injury-site, serum, dorsal root ganglia (DRG) and/or spinal cord. We further tested whether estrogen effects on cytokine levels are in part mediated through hypothalamic-pituitary-adrenal (1-IPA) axis activation. Lumbar DRG, spinal cord, serum, and hind paw tissue were analyzed for cytokine levels in 17 beta-estradiol-(20%) or vehicle-(100% cholesterol) treated female rats following ovariectomy/sham adrenalectomy (OVX), adrenalectomy/sham ovariectomy (ADX) or ADX + OVX operation at baseline and post formalin injection. Formalin significantly increased proinflammatory interleukin (IL)-6 levels in the paw, as well as pro- and anti-inflammatory cytokine levels in the DRG, spinal cord and serum in comparison to naive conditions. Estrogen replacement significantly increased anti-inflammatory IL-10 levels in the DRG. Centrally, estradiol significantly decreased proinflammatory tumor necrosis factor (TNF)-alpha and IL-10 levels, as well as IL-10 levels, in the spinal cord in comparison to cholesterol treatment. At both sites, most estradiol modulatory effects occurred irrespective of pain or surgical condition. Estradiol alone had no influence on cytokine release in the paw or serum, indicating that estrogen effects were site-specific. Although cytokine levels were altered between surgical conditions at baseline and following formalin administration, ADX operation did not significantly reverse estradiol's modulation of cytokine levels. These results suggest that estrogen directly regulates cytokines independent of HPA axis activity in vivo, in part by reducing cytokine levels in the spinal cord. (C) 2015 Published by Elsevier Ltd.
机译：尽管雌激素可减轻炎症介导的疼痛反应，但其作用机理尚不清楚。这项研究调查了雌激素是否通过降低基线或损伤部位，血清，背根神经节（DRG）和/或脊髓中炎症诱导的细胞因子水平来调节炎症信号传导。我们进一步测试了雌激素对细胞因子水平的影响是否部分通过下丘脑-垂体-肾上腺（1-IPA）轴激活介导。在经卵巢切除/假手术肾上腺切除术（OVX），肾上腺切除术/假手术后，分析了17只经β-雌二醇（20％）或媒介物（100％胆固醇）治疗的雌性大鼠的腰DRG，脊髓，血清和后爪组织的细胞因子水平。在基线和福尔马林注射后进行卵巢切除术（ADX）或ADX + OVX手术。与幼稚条件相比，福尔马林显着增加了爪中促炎性白介素（IL）-6的水平，以及DRG，脊髓和血清中促炎和抗炎细胞因子的水平。雌激素替代显着增加了DRG中的抗炎IL-10水平。与胆固醇治疗相比，雌二醇在中枢上显着降低了脊髓中促炎性肿瘤坏死因子（TNF）-α和IL-10的水平，以及IL-10的水平。在两个部位，大多数雌二醇调节作用均发生，与疼痛或手术情况无关。单独的雌二醇对爪或血清中细胞因子的释放没有影响，表明雌激素的作用是部位特异性的。尽管在基线和福尔马林给药后的手术条件之间细胞因子水平发生了变化，但ADX手术并未显着逆转雌二醇对细胞因子水平的调节。这些结果表明，雌激素部分地通过降低脊髓中的细胞因子水平而直接调节细胞因子，而与体内HPA轴活性无关。 （C）2015由Elsevier Ltd.出版

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