Acute stress suppresses pro-inflammatory cytokines TNF-α and IL-1β independent of a catecholamine-driven increase in IL-10 production
Acute stress suppresses pro-inflammatory cytokines TNF-α and IL-1β independent of a catecholamine-driven increase in IL-10 production
复制标题
DOI：
10.1016/j.jneuroim.2004.10.016
复制
发表时间：
2005-02-01
影响因子：
3.3
通讯作者：
Harkin, A
中科院分区：
文献类型：
--
作者：
Connor, TJ;Brewer, C;Harkin, A
白细胞介素（IL）-10是一种抗炎细胞因子，可以下调免疫应答的各个方面。在这项研究中，我们表明，暴露于心理生理应激（游泳应激）增加IL-10的生产在雌性大鼠在体内的挑战与细菌脂多糖（LPS）。LPS诱导的IL-10的增加与促炎细胞因子IL-1 β和TNF-α的抑制有关，表明总体而言，游泳应激促进了免疫抑制细胞因子表型。尽管IL-10抑制促炎细胞因子产生的能力得到了充分的证明，但IL-10的中和作用未能阻断应激诱导的IL-1 β和TNF-α抑制。这些数据表明，游泳应激对这些促炎细胞因子的抑制作用发生。独立于增加的IL-10产生。为了确定游泳应激诱导的免疫抑制是否由交感神经系统活动增加和随后的β-肾上腺素受体激活介导，我们评估了β-肾上腺素受体拮抗剂纳多洛尔阻断应激诱导的细胞因子产生变化的能力。虽然用纳多洛尔预处理完全阻断了应激诱导的IL-10增加，但它未能改变TNF-α或IL-1 β的抑制。同样地，用糖皮质激素受体拮抗剂米非司酮预处理也不能减弱游泳应激对IL-1 β和TNF-α产生的抑制作用。这些数据表明，无论是增加糖皮质激素分泌，也不是儿茶酚胺诱导的β-肾上腺素受体激活，介导的抑制作用的游泳应激促炎细胞因子的产生。总之，这些数据证明了β-肾上腺素受体活化在急性游泳应激增加LPS诱导的IL-10产生的能力中的作用，并且还突出了游泳应激增加IL-10和抑制促炎细胞因子产生的能力之间的机械分离。(C)2004 Elsevier B. V.保留所有权利。
Interleukin (IL)-10 is an anti-inflammatory cytokine that can down-regulate various aspects of the immune response. In this study we demonstrate that exposure to a psychophysiological stressor (swim stress) increases IL-10 production in female rats in response to an in vivo challenge with bacterial lipopolysaccharide (LPS). This increase in LPS-induced IL-10 was associated with suppression of the proinflammatory cytokines IL-1beta and TNF-alpha, indicating that overall, swim stress promotes an immunosuppressive cytokine phenotype. Despite the well-documented ability of IL-10 to suppress pro-inflammatory cytokine production, neutralisation of IL-10 failed to block the stress-induced suppression of IL-1beta and TNF-alpha. These data indicate that the suppressive effect of swim stress on these pro-inflammatory cytokines occurs. independently of increased IL-10 production. To determine if swim stress-induced immunosuppression was mediated by increased sympathetic nervous system activity, and subsequent p-adrenoceptor activation, we assessed the ability of the beta-adrenoceptor antagonist nadolol to block stressor-induced changes in cytokine production. Whilst pre-treatment with nadolol completely blocked the stress-induced increase in IL-10, it failed to alter the suppression of TNF-alpha or IL-1beta. Similarly, pre-treatment with the glucocorticoid receptor antagonist mifepristone also failed to attenuate the suppressive effect of swim stress on IL-1beta and TNF-alpha production. These data indicate that neither increased glucocorticoid secretion, nor catecholamine-induced beta-adrenoceptor activation, mediates the suppressive effect of swim stress on pro-inflammatory cytokine production. Taken together, these data demonstrate a role for beta-adrenoceptor activation in the ability of acute swim stress to increase LPS-induced IL-10 production, and also highlight a mechanistic dissociation between the ability of swim stress to increase IL-10 and suppress pro-inflammatory cytokine production. (C) 2004 Elsevier B.V. All rights reserved.