Relationship between interleukin (IL)-6 and hypothalamic-pituitary-adrenocortico-axis hormones in rheumatoid arthritis

Journal/Book: Z Rheumatol 1999; 58: 304. 1999;

Abstract: G. Mastorakos; Endocrine Unit Evgenidion Hospital - Athens University Athens Systemic symptoms in rheumatoid arthritis (RA) are mediated at last in part by elevated levels of circulating interleukin (IL)-6. In the past we have shown that this cytokine is a potent activator of the human hypothalamic-pituitary-adrenal (HPA) axis. This activation is both hypothalamic corticotropin-releasing hormone (CRH)- and vasopressin (AVP)- mediated. To evaluate the 24-h circadian secretory dynamics of ACTH cortisol and IL-6 and their interactions in patients with early untreated RA we recruited and studied five newly diagnosed untreated RA patients early in the course of their disease and five age- gender- and race-matched control subjects. We collected serial blood samples over 24 h and measured plasma ACTH and cortisol every 30 min and IL-6 every hour. The 24-h collection was followed by administration of ovine CRH (oCRH) and post-oCRH serial blood samples over 2 h. We analyzed the 24-h overall levels of these hormones and their circadian variations and performed time-lagged cross-correlation analyses among them. The untreated RA patients had 24 h timeintegrated plasma ACTH plasma cortisol levels and urinary free cortisol excretion that were not significantly different from control subjects in spite of their disease activity. However an earlier morning surge of plasma ACTH and cortisol in the patients was suggested. Plasma ACTH and cortisol responses to oCRH were similar in RA patients and controls. IL-6 levels were significantly increased in the RA patients compared with control subjects during the early morning hours (P<0.05). There was pronounced circadian variation of plasma IL-6 levels. In the RA patients we detected a positive temporal correlation between plasma levels of IL-6 and ACTH/cortisol with elevated levels of IL-6 before the elevation of ACTH and cortisol by 1 and 2 h respectively. ... le

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