Stephanou A, Sarlis N J, Knight R A, Lightman S L, Chowdrey H S
Neuroendocrinology Unit, Charing Cross and Westminster Medical School, Charing Cross Hospital, London, UK.
J Neuroimmunol. 1992 Dec;41(2):215-22. doi: 10.1016/0165-5728(92)90072-s.
In the rat, adjuvant arthritis (AA) is an inflammatory joint disease associated with chronic stimulation of the hypothalamic-pituitary-adrenal (HPA) axis. We have investigated the effects of the immunosuppressive agent cyclosporine A (CsA) on plasma levels of adrenocorticotropin (ACTH) and corticosterone (B), as well as on anterior pituitary proopiomelanocortin (POMC) and interleukin (IL)-6 mRNA accumulation in control and adjuvant-injected animals. In control animals, CsA reduced basal anterior pituitary POMC and IL-6 mRNA and decreased plasma levels of ACTH and B. Adjuvant-injected animals that were treated with CsA showed no clinical signs of AA. Moreover, CsA inhibited the arthritis-induced increases in pituitary POMC and IL-6 mRNA levels and in circulating ACTH and B. In vitro, CsA reduced the POMC mRNA content of cultured anterior pituitary cells and diminished the stimulatory effects of corticotropin-releasing hormone (CRH) on POMC mRNA expression and ACTH secretion from these cells. These data indicate that CsA has a direct action on the HPA axis and also reduces the activation of the HPA axis seen in chronic inflammatory arthritis.
在大鼠中，佐剂性关节炎（AA）是一种与下丘脑 - 垂体 - 肾上腺（HPA）轴慢性刺激相关的炎性关节疾病。我们研究了免疫抑制剂环孢素A（CsA）对对照组和注射佐剂动物血浆促肾上腺皮质激素（ACTH）和皮质酮（B）水平的影响，以及对垂体前叶阿黑皮素原（POMC）和白细胞介素（IL）-6 mRNA积累的影响。在对照动物中，CsA降低了垂体前叶基础POMC和IL-6 mRNA水平，并降低了ACTH和B的血浆水平。用CsA治疗的注射佐剂动物未表现出AA的临床症状。此外，CsA抑制了关节炎诱导的垂体POMC和IL-6 mRNA水平以及循环ACTH和B的升高。在体外，CsA降低了培养的垂体前叶细胞的POMC mRNA含量，并减弱了促肾上腺皮质激素释放激素（CRH）对这些细胞POMC mRNA表达和ACTH分泌的刺激作用。这些数据表明CsA对HPA轴有直接作用，并且还减少了在慢性炎症性关节炎中观察到的HPA轴的激活。
