Amelioration of murine antigen-induced arthritis by dehydroepiandrosterone (DHEA).
OBJECTIVE
Sex hormones have immunomodulatory properties and may play an important role in the pathogenesis of autoimmune diseases like rheumatoid arthritis (RA). This study sought to examine the effects of the natural weak androgen dehydroepiandrosterone (DHEA) and its metabolite androstenediol (AED) on the development of murine antigen-induced arthritis (AIA).


METHODS
DHEA and AED were administered orally, approximately 10 mg/day, from the time of AIA induction (i.e., 3 weeks after start of immunization) in young male as well as young and old female C57BL/6 mice. The effects were assessed in terms of joint swelling, histological changes, and cell-mediated and humoral immunity.


RESULTS
Compared to untreated AIA animals, continuous administration of DHEA decreased knee joint swelling during acute and chronic AIA, as well as histological signs of inflammation and joint destruction during chronic AIA. These effects were age- and gender-independent. Delayed-type hypersensitivity (DTH) to the specific antigen methylated bovine serum albumin (mBSA) was significantly reduced, but there were no changes in the balance of the T helper (Th) cell subsets Th1/Th2, as tested by the ratio of IgG isotypes in the sera. Whereas serum levels of IgG antibodies to mBSA were not influenced, the formation of IgG autoantibodies to the matrix constituents collagen type I, collagen type II, and cartilage proteoglycans was significantly inhibited. In all experiments, the effects of AED were not significantly stronger than those of DHEA.


CONCLUSIONS
Administration of exogenous DHEA ameliorates the severity of acute and chronic AIA, presumably by suppressing cell-mediated immunity against mBSA (the inducing antigen) and formation of autoantibodies. However, because of the fundamentally different DHEA physiology in rodents, the role of such a replacement therapy in human RA deserves further elucidation.
Röntzsch
A
A
Institute of Pathology, Friedrich Schiller University, Ziegelmühlenweg 1, 07740 Jena, Germany.
Thoss
K
K
Petrow
P K
PK
Henzgen
S
S
Bräuer
R
R
D000276:Adjuvants, Immunologic / Q000627:therapeutic use*; D015114:Androstenediol / Q000627:therapeutic use*; D000818:Animals; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology; D024042:Collagen Type I / Q000276:immunology; D024043:Collagen Type II / Q000276:immunology; D003687:Dehydroepiandrosterone / Q000627:therapeutic use*; D005260:Female; D006968:Hypersensitivity, Delayed / Q000209:etiology / Q000517:prevention & control; D007111:Immunity, Cellular / Q000187:drug effects; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011509:Proteoglycans / Q000276:immunology; D012710:Serum Albumin, Bovine; D012720:Severity of Illness Index
D000276:Adjuvants, Immunologic; D000888:Antibodies, Anti-Idiotypic; D024042:Collagen Type I; D024043:Collagen Type II; D007074:Immunoglobulin G; D011509:Proteoglycans; C029180:methylated bovine serum albumin; D012710:Serum Albumin, Bovine; D003687:Dehydroepiandrosterone; D015114:Androstenediol