Circadian Relationships between Interleukin (IL)-6 and Hypothalamic-Pituitary-Adrenal Axis Hormones: Failure of IL-6 to Cause Sustained Hypercortisolism in Patients with Early Untreated Rheumatoid Arthritis
Systemic symptoms in rheumatoid arthritis (RA) are mediated, at least in part, by elevated levels of circulating interleukin (IL)-6, and this cytokine is also a potent stimulus of the hypothalamic-pituitary-adrenal axis. To evaluate the 24-h circadian secretory dynamics of ACTH, cortisol, and IL-6 a...
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Veröffentlicht in: | The journal of clinical endocrinology and metabolism 1997-04, Vol.82 (4), p.1279-1283 |
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Sprache: | eng |
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Zusammenfassung: | Systemic symptoms in rheumatoid arthritis (RA) are mediated, at least
in part, by elevated levels of circulating interleukin (IL)-6, and this
cytokine is also a potent stimulus of the
hypothalamic-pituitary-adrenal axis. 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 time-integrated 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 elevations of
ACTH and cortisol by 1 and 2 h, respectively. In the same
patients, we detected a negative effect of cortisol upon IL-6 exerted
with a delay of 5 h. The data presented here suggest that although
endogenous IL-6 may stimulate secretion of ACTH and cortisol, overall
activity of the hypothalamic-pituitary-adrenal axis remains normal and
apparently is insufficient to inhibit ongoing inflammation in early
untreated RA patients. |
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ISSN: | 0021-972X 1945-7197 |
DOI: | 10.1210/jcem.82.4.3852 |