Morand E F, Leech M
Centre for Inflammatory Diseases, Department of Medicine, Monash University, Monash Medical Centre, Clayton, Victoria, Australia.
Immunol Cell Biol. 2001 Aug;79(4):395-9. doi: 10.1046/j.1440-1711.2001.01028.x.
The profound anti-inflammatory effects of glucocorticoids in drug therapy are reflected in the effects in vivo of endogenous glucocorticoids produced by the adrenals. The production of adrenal glucocorticoids is driven by the hypothalamus and pituitary, which in turn are responsive to circulating products of the inflammatory response, especially cytokines. That inflammation can drive the production of anti-inflammatory glucocorticoids denotes the hypothalamic-pituitary-adrenal (HPA)-immune axis as a classic negative feedback control loop. Defects in HPA axis function are implicated in susceptibility to, and severity of, animal models of rheumatoid arthritis (RA), and are hypothesized to contribute to the human disease. In this paper, data supporting the concept of the HPA axis as a regulator of the inflammatory response in animal models of arthritis are reviewed, along with data from studies in humans. Taken together, these data support the hypothesis that the HPA axis provides one of the key mechanisms for inhibitory regulation of the inflammatory response. Manipulation of HPA axis-driven endogenous anti-inflammatory responses may provide new methods for the therapeutic control of inflammatory diseases.
糖皮质激素在药物治疗中具有显著的抗炎作用，这体现在肾上腺产生的内源性糖皮质激素的体内效应上。肾上腺糖皮质激素的产生受下丘脑和垂体驱动，而下丘脑和垂体又对炎症反应的循环产物，尤其是细胞因子作出反应。炎症能够驱动抗炎性糖皮质激素的产生，这表明下丘脑 - 垂体 - 肾上腺（HPA）-免疫轴是一个经典的负反馈控制回路。HPA轴功能缺陷与类风湿性关节炎（RA）动物模型的易感性和严重程度有关，并且据推测对人类疾病也有影响。在本文中，我们回顾了支持HPA轴作为关节炎动物模型中炎症反应调节因子这一概念的数据，以及来自人类研究的数据。综合来看，这些数据支持了以下假设：HPA轴为炎症反应的抑制性调节提供了关键机制之一。操纵HPA轴驱动的内源性抗炎反应可能为炎症性疾病的治疗控制提供新方法。
