Straub, Rainer H. and Haerle, Peter and Yamana, Seizo and Matsuda, Takemasa and Takasugi, Kiyoshi and Kishimoto, Tadarnitsu and Nishimoto, Norihiro (2006) Anti-interleukin-6 receptor antibody therapy favors adrenal androgen secretion in patients with rheumatoid arthritis - A randomized, double-blind, placebo-controlled study. ARTHRITIS AND RHEUMATISM, 54 (6). pp. 1778-1785. ISSN 0004-3591, 1529-0131
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Objective. Proinflammatory cytokines such as tumor necrosis factor (TNF) were demonstrated to inhibit adrenal steroidogenesis in patients with rheumatoid arthritis (RA), and this was particularly evident in the increase in adrenal androgen levels during anti-TNF therapy. This study investigated the influence on steroidogenesis of an interleukin-6 (IL-6)-neutralizing strategy using IL-6 receptor monoclonal antibodies (referred to as MRA). Methods. In a placebo-controlled, double-blind, randomized study over 12 weeks in 29 patients with RA being treated with prednisolone, 13 of whom received placebo and 16 of whom received 8 mg MRA/kg body weight, the effects of MRA on serum levels of adrenocorticotropic hormone (ACTH), cortisol, 17-hydroxyprogesterone (17OHP), dehydroepiandrosterone (DHEA), DHEA sulfate (DHEAS), andro-stenedione (ASD), estrone, and 17 ss-estradiol, as well as their respective molar ratios, were determined. Results. MRA therapy markedly improved clinical signs of inflammation (the erythrocyte sedimentation rate, swollen joint score, and Disease Activity Score in 28 joints). Serum levels of ACTH and cortisol and the molar ratio of cortisol to ACTH did not change. Although serum levels of DHEA and DHEAS remained stable during therapy, the DHEAS:DHEA molar ratio significantly decreased in treated patients (P = 0.048). Serum levels of ASD as well as the ASD:cortisol and ASD:17OHP molar ratios increased in MRA-treated patients (minimum P < 0.004). Serum levels of estrone and 17 ss-estradiol did not change. but the estrone:ASD molar ratio (an indicator of aromatization) decreased during 12 weeks of MRA treatment (P = 0.001). Conclusion. Neutralization of IL-6 increases secretion of biologically active adrenal androgens in relation to that of precursor hormones and estrogens. This is another important indication that proinflammatory cytokines interfere with adrenal androgen steroidogenesis in patients with RA.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-NECROSIS-FACTOR; BLOOD MONONUCLEAR-CELLS; BREAST FIBROBLASTS; ESTROGEN FORMATION; AROMATASE-ACTIVITY; GROWTH-FACTORS; FACTOR-ALPHA; MCF-7 CELLS; IN-VITRO; INTERLEUKIN-6; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 15 Feb 2021 06:04 |
| Last Modified: | 15 Feb 2021 06:04 |
| URI: | https://pred.uni-regensburg.de/id/eprint/34459 |
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