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

Volumn 54, Issue 6, 2006, Pages 1778-1785

  Straub, Rainer H ^a   Härle, Peter ^a   Yamana, Seizo ^b   Matsuda, Takemasa ^c   Takasugi, Kiyoshi ^d   Kishimoto, Tadamitsu ^e   Nishimoto, Norihiro ^e  

^a UNIVERSITY HOSPITAL REGENSBURG   (Germany)

^b Hiroshima Memorial Hospital   (Japan)

^c Kagoshima Red Cross Hospital   (Japan)

^d Dohgo Spa Hospital   (Japan)

^e OSAKA UNIVERSITY   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

ANDROGEN; ANDROSTENEDIONE; CORTICOTROPIN; CYTOKINE; ESTRADIOL; ESTRONE; HYDROCORTISONE; HYDROXYPROGESTERONE; INTERLEUKIN 6; INTERLEUKIN 6 RECEPTOR; INTERLEUKIN 6 RECEPTOR ANTIBODY; MONOCLONAL ANTIBODY; PRASTERONE; PRASTERONE SULFATE; RECEPTOR ANTIBODY; UNCLASSIFIED DRUG;

ADRENAL DISEASE; ADULT; AGED; ANDROGEN SYNTHESIS; ARTICLE; CLINICAL ARTICLE; CLINICAL TRIAL; CONTROLLED CLINICAL TRIAL; CONTROLLED STUDY; DISEASE ACTIVITY; DRUG EFFECT; DRUG EFFICACY; ERYTHROCYTE SEDIMENTATION RATE; FEMALE; HUMAN; INFLAMMATION; JOINT SWELLING; MALE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; RHEUMATOID ARTHRITIS; SCORING SYSTEM;

17-ALPHA-HYDROXYPROGESTERONE; ADRENAL GLANDS; ADRENOCORTICOTROPIC HORMONE; ADULT; AGED; ANDROGENS; ANDROSTENEDIONE; ANTIBODIES, MONOCLONAL; ARTHRITIS, RHEUMATOID; DEHYDROEPIANDROSTERONE; DEHYDROEPIANDROSTERONE SULFATE; DOUBLE-BLIND METHOD; ESTRADIOL; ESTRONE; FEMALE; HUMANS; HYDROCORTISONE; MALE; MIDDLE AGED; PREDNISOLONE; RECEPTORS, INTERLEUKIN-6;

EID: 33745027354     PISSN: 00043591     EISSN: None     Source Type: Journal    
DOI: 10.1002/art.21826     Document Type: Article

References (43)

1. Ehrhart-Bornstein M, Hinson JP, Bornstein SR, Scherbaum WA, Vinson GP. Intraadrenal interactions in the regulation of adrenocortical steroidogenesis. Endocr Rev 1998;19:101-43.
2. Herrmann M, Schölmerich J, Straub RH. Influence of cytokines and growth factors on distinct steroidogenic enzymes in vitro: a short tabular data collection. Ann N Y Acad Sci 2002;966:166-86.
3. Jaattela M, Ilvesmaki V, Voutilainen R, Stenman UH, Saksela E. Tumor necrosis factor as a potent inhibitor of adrenocorticotropin-induced cortisol production and steroidogenic P450 enzyme gene expression in cultured human fetal adrenal cells. Endocrinology 1991;128:623-9.
4. Hennebold JD, Daynes RA. Regulation of macrophage dehydroepiandrosterone sulfate metabolism by inflammatory cytokines. Endocrinology 1994;135:67-75.
5. Weidler C, Struharova S, Schmidt M, Ugele B, Scholmerich J, Straub RH. Tumor necrosis factor inhibits conversion of dehydroepiandrosterone sulfate (DHEAS) to DHEA in rheumatoid arthritis synovial cells: a prerequisite for local androgen deficiency. Arthritis Rheum 2005;52:1721-9.
6. Bethin KE, Vogt SK, Muglia LJ. Interleukin-6 is an essential, corticotropin-releasing hormone-independent stimulator of the adrenal axis during immune system activation. Proc Natl Acad Sci U S A 2000;97:9317-22.
7. Castagnetta LA, Carruba G, Granata OM, Stefano R, Miele M, Schmidt M, et al. Increased estrogen formation and estrogen to androgen ratio in the synovial fluid of patients with rheumatoid arthritis. J Rheumatol 2003;30:2597-605.
8. Cutolo M, Lahita RG. Estrogens and arthritis. Rheum Dis Clin North Am 2005;31:19-27.
9. Adams EF, Rafferty B, White MC. Interleukin 6 is secreted by breast fibroblasts and stimulates 17β-oestradiol oxidoreductase activity of MCF-7 cells: possible paracrine regulation of breast 17β-oestradiol levels. Int J Cancer 1991;49:118-21.
10. Duncan LJ, Reed MJ. The role and proposed mechanism by which oestradiol 17β- hydroxysteroid dehydrogenase regulates breast tumour oestrogen concentrations. J Steroid Biochem Mol Biol 1995;55:565-72.
11. Elliott MJ, Maini RN, Feldmann M, Long-Fox A, Charles P, Katsikis P, et al. Treatment of rheumatoid arthritis with chimeric monoclonal antibodies to tumor necrosis factor α. Arthritis Rheum 1993;36:1681-90.
12. Braun J, Brandt J, Listing J, Zink A, Alten R, Golder W, et al. Treatment of active ankylosing spondylitis with infliximab: a randomised controlled multicentre trial. Lancet 2002;359:1187-93.
13. Nishimoto N, Yoshizaki K, Miyasaka N, Yamamoto K, Kawai S, Takeuchi T, et al. Treatment of rheumatoid arthritis with humanized anti-interleukin-6 receptor antibody: a multicenter, double-blind, placebo-controlled trial. Arthritis Rheum 2004;50:1761-9.
14. Straub RH, Pongratz G, Schölmerich J, Kees F, Schaible TF, Antoni C, et al. Long-term anti-tumor necrosis factor antibody therapy in rheumatoid arthritis patients sensitizes the pituitary gland and favors adrenal androgen secretion. Arthritis Rheum 2003;48:1504-12.
15. Sato K, Tsuchiya M, Saldanha J, Koishihara Y, Ohsugi Y, Kishimoto T, et al. Reshaping a human antibody to inhibit the interleukin 6-dependent tumor cell growth. Cancer Res 1993;53:851-6.
16. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF, Cooper NS, et al. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988;31:315-24.
17. Straub RH, Konecna L, Hrach S, Rothe G, Kreutz M, Schölmerich J, et al. Serum dehydroepiandrosterone (DHEA) and DHEA sulfate are negatively correlated with serum interleukin-6 (IL-6), and DHEA inhibits IL-6 secretion from mononuclear cells in man in vitro: possible link between endocrinosenescence and immunosenescence. J Clin Endocrinol Metab 1998;83:2012-7.
18. Anderson DC, Yen SS. Effects of estrogens on adrenal 3β- hydroxysteroid dehydrogenase in ovariectomized women. J Clin Endocrinol Metab 1976;43:561-70.
19. Barone RM, Shamonki IM, Siiteri PK, Judd HL. Inhibition of peripheral aromatization of androstenedione to estrone in postmenopausal women with breast cancer using delta 1-testololactone. J Clin Endocrinol Metab 1979;49:672-6.
20. Mastorakos G, Chrousos GP, Weber JS. Recombinant interleukin-6 activates the hypothalamic-pituitary-adrenal axis in humans. J Clin Endocrinol Metab 1993;77:1690-4.
21. Spath-Schwalbe E, Born J, Schrezenmeier H, Bornstein SR, Stromeyer P, Drechsler S, et al. Interleukin-6 stimulates the hypothalamus-pituitary- adrenocortical axis in man. J Clin Endocrinol Metab 1994;79:1212-4.
22. Franchimont D, Bouma G, Galon J, Wolkersdorfer GW, Haidan A, Chrousos GP, et al. Adrenal cortical activation in murine colitis. Gastroenterology 2000;119:1560-8.
23. Reed MJ, Topping L, Coldham NG, Purohit A, Ghilchik MW, James VH. Control of aromatase activity in breast cancer cells: the role of cytokines and growth factors. J Steroid Biochem Mol Biol 1993;44:589-96.
24. Macdiarmid F, Wang D, Duncan LJ, Purohit A, Ghilchick MW, Reed MJ. Stimulation of aromatase activity in breast fibroblasts by tumor necrosis factor α. Mol Cell Endocrinol 1994;106:17-21.
25. Zhao Y, Agarwal VR, Mendelson CR, Simpson ER. Transcriptional regulation of CYP19 gene (aromatase) expression in adipose stromal cells in primary culture. J Steroid Biochem Mol Biol 1997;61:203-10.
26. Danenberg HD, Alpert G, Lustig S, Ben-Nathan D. Dehydroepiandrosterone protects mice from endotoxin toxicity and reduces tumor necrosis factor production. Antimicrob Agents Chemother 1992;36:2275-9.
27. Daynes RA, Araneo BA, Ershler WB, Maloney C, Li GZ, Ryu SY. Altered regulation of IL-6 production with normal aging: possible linkage to the age-associated decline in dehydroepiandrosterone and its sulfated derivative. J Immunol 1993;150:5219-30.
28. Li ZG, Danis VA, Brooks PM. Effect of gonadal steroids on the production of IL-1 and IL-6 by blood mononuclear cells in vitro. Clin Exp Rheumatol 1993;11:157-62.
29. Cutolo M, Accardo S, Villaggio B, Barone A, Sulli A, Balleari E, et al. Androgen metabolism and inhibition of interleukin-1 synthesis in primary cultured human synovial macrophages. Mediat Inflam 1995;4:138-45.
30. Kanda N, Tsuchida T, Tamaki K. Testosterone inhibits immunoglobulin production by human peripheral blood mononuclear cells. Clin Exp Immunol 1996;106:410-5.
31. Kanda N, Tsuchida T, Tamaki K. Testosterone suppresses anti-DNA antibody production in peripheral blood mononuclear cells from patients with systemic lupus erythematosus. Arthritis Rheum 1997;40:1703-11.
32. Keller ET, Chang C, Ershler WB. Inhibition of NFκB activity through maintenance of IκBα levels contributes to dihydrotestosterone- mediated repression of the interleukin-6 promoter. J Biol Chem 1996;271:26267-75.
33. Toyoda H, Takei S, Formby B. Effect of 5-α dihydrotestosterone on T-cell proliferation of the female nonobese diabetic mouse. Proc Soc Exp Biol Med 1996;213:287-93.
34. Cutolo M, Balleari E, Giusti M, Intra E, Accardo S. Androgen replacement therapy in male patients with rheumatoid arthritis. Arthritis Rheum 1991;34:1-5.
35. Booji A, Biewenga-Booji CM, Huber-Bruning O, Cornelis C, Jacobs JW, Bijlsma JW. Androgens as adjuvant treatment in postmenopausal female patients with rheumatoid arthritis. Ann Rheum Dis 1996;55:811-5.
36. Cutolo M, Wilder R. Different roles for androgens and estrogens in the susceptibility to autoimmune rheumatic diseases. Rheum Dis Clin North Am 2000;26:825-39.
37. Schmidt M, Weidler C, Naumann H, Scholmerich J, Straub RH. Androgen conversion in osteoarthritis and rheumatoid arthritis synoviocytes: androstenedione and testosterone inhibit estrogen formation and favor production of more potent 5α-reduced androgens. Arthritis Res Ther 2005;7:R938-48.
38. Straub RH, Lehle K, Herfarth H, Weber M, Falk W, Preuner J, et al. Dehydroepiandrosterone in relation to other adrenal hormones during an acute inflammatory stressful disease state compared with chronic inflammatory disease: role of interleukin-6 and tumour necrosis factor. Eur J Endocrinol 2002;146:365-74.
39. Duncan LJ, Coldham NG, Reed MJ. The interaction of cytokines in regulating oestradiol 17β-hydroxysteroid dehydrogenase activity in MCF-7 cells. J Steroid Biochem Mol Biol 1994;49:63-8.
40. Yokota S, Miyamae T, Imagawa T, Iwata N, Katakura S, Mori M, et al. Therapeutic efficacy of humanized recombinant anti-interleukin-6 receptor antibody in children with systemic-onset juvenile idiopathic arthritis. Arthritis Rheum 2005;52:818-25.
41. Ito H, Takazoe M, Fukuda Y, Hibi T, Kusugami K, Andoh A, et al. A pilot randomized trial of a human anti-interleukin-6 receptor monoclonal antibody in active Crohn's disease. Gastroenterology 2004;126:989-96.
42. Mihara M, Nishimoto N, Ohsugi Y. The therapy of autoimmune diseases by anti-interleukin-6 receptor antibody. Expert Opin Biol Ther 2005;5:683-90.
43. Bellido T, Jilka RL, Boyce BF, Girasole G, Broxmeyer H, Dalrymple SA, et al. Regulation of interleukin-6, osteoclastogenesis, and bone mass by androgens: the role of the androgen receptor. J Clin. Invest 1995;95:2886-95.