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Anti-interleukin-6 receptor antibody therapy favors adrenal androgen secretion in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled study.
Arthritis Rheum. 2006 Jun; 54(6):1778-85.AR

Abstract

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), androstenedione (ASD), estrone, and 17beta-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 17beta-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.

Authors+Show Affiliations

University Hospital Regensburg, Regensburg, Germany. rainer.straub@klinik.uni-regensburg.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16729287

Citation

Straub, Rainer H., et al. "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, vol. 54, no. 6, 2006, pp. 1778-85.
Straub RH, Härle P, Yamana S, et al. Anti-interleukin-6 receptor antibody therapy favors adrenal androgen secretion in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2006;54(6):1778-85.
Straub, R. H., Härle, P., Yamana, S., Matsuda, T., Takasugi, K., Kishimoto, T., & Nishimoto, N. (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), 1778-85.
Straub RH, et al. Anti-interleukin-6 Receptor Antibody Therapy Favors Adrenal Androgen Secretion in Patients With Rheumatoid Arthritis: a Randomized, Double-blind, Placebo-controlled Study. Arthritis Rheum. 2006;54(6):1778-85. PubMed PMID: 16729287.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-interleukin-6 receptor antibody therapy favors adrenal androgen secretion in patients with rheumatoid arthritis: a randomized, double-blind, placebo-controlled study. AU - Straub,Rainer H, AU - Härle,Peter, AU - Yamana,Seizo, AU - Matsuda,Takemasa, AU - Takasugi,Kiyoshi, AU - Kishimoto,Tadamitsu, AU - Nishimoto,Norihiro, PY - 2006/5/27/pubmed PY - 2006/7/15/medline PY - 2006/5/27/entrez SP - 1778 EP - 85 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 54 IS - 6 N2 - 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), androstenedione (ASD), estrone, and 17beta-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 17beta-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. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/16729287/Anti_interleukin_6_receptor_antibody_therapy_favors_adrenal_androgen_secretion_in_patients_with_rheumatoid_arthritis:_a_randomized_double_blind_placebo_controlled_study_ L2 - https://doi.org/10.1002/art.21826 DB - PRIME DP - Unbound Medicine ER -