Harbuz M S, Korendowych E, Jessop D S, Crown A L, Li pdfan S L, Kirwan J R
University Research Centre for Neuroendocrinology, University of Bristol, Bristol Royal Infirmary, Marlborough Street, Bristol BS2 8HW, UK.
J Endocrinol. 2003 Jul;178(1):55-60. doi: 10.1677/joe.0.1780055.
A defective hypothalamo-pituitary-adrenal axis response to inflammatory cytokines may contribute to the pathophysiology of rheumatoid arthritis (RA). The purpose of this study was to define further the mechanisms responsible for this dysregulation. Six normal individuals and seven patients with active RA were recruited and given an oral dose of dexamethasone at 2300 h the evening before the study. The next day, an i.v. catheter was fitted at 1300 h. Blood samples were collected between 1400 h and 1700 h before and after infusion (at 1500 h) of corticotrophin releasing factor (CRF). Plasma was separated and stored at-20 degrees C before radioimmunoassay for ACTH, cortisol and dihydroepiandrosterone (DHEA). Before the CRF challenge, ACTH and cortisol were significantly increased and DHEA significantly decreased in the patients with RA compared with the controls. Neither ACTH nor DHEA was significantly altered after CRF infusion. Control individuals did not mount a cortisol response to infusion of CRF. Similarly, four of the patients with RA did not respond to CRF. However, in contrast to the controls, three of the patients mounted an immediate and sustained cortisol response after receiving CRF. These data reveal that three of the seven patients with RA were able to escape from dexamethasone suppression and mount a cortisol response to CRF challenge. This suggests that there may be a subpopulation of patients with RA who have impaired glucocorticoid feedback. The implications of this alteration for disease progression remain to be determined.
下丘脑 - 垂体 - 肾上腺轴对炎性细胞因子的反应缺陷可能与类风湿关节炎（RA）的病理生理学有关。本研究的目的是进一步明确导致这种调节异常的机制。招募了6名正常个体和7名活动性RA患者，在研究前一天晚上23:00口服地塞米松。第二天，13:00插入静脉导管。在输注促肾上腺皮质激素释放因子（CRF）之前（14:00）和之后（15:00输注，17:00）采集血样。分离血浆并在-20℃保存，然后进行促肾上腺皮质激素（ACTH）、皮质醇和脱氢表雄酮（DHEA）的放射免疫测定。在CRF激发前，与对照组相比，RA患者的ACTH和皮质醇显著升高，DHEA显著降低。CRF输注后，ACTH和DHEA均无显著变化。对照个体对CRF输注未产生皮质醇反应。同样，4名RA患者对CRF无反应。然而，与对照组不同的是，3名患者在接受CRF后出现了即时且持续的皮质醇反应。这些数据表明，7名RA患者中有3名能够摆脱地塞米松抑制，并对CRF激发产生皮质醇反应。这表明可能存在一部分糖皮质激素反馈受损的RA患者。这种改变对疾病进展的影响尚待确定。
