Reduction in the incidence and severity of collagen‐induced arthritis in DBA/1 mice, using exogenous dehydroepiandrosterone

Abstract

Objective. This study examined the effect of exogenous dehydroepiandrosterone (DHEA) on the onset, incidence, and severity of collagen-induced arthritis (CIA).Methods. DHEA was administered subcutaneously prior to arthritis induction in DBN1 mice, and the severity of the subsequent arthritis was monitored. Serum levels of total IgG and IgG isotype-specific anti-murine type I1 collagen were measured.Results. Repeated administration of DHEA during arthritis induction delayed the onset and decreased the severity of arthritis in male and female DBN1 mice. DHEA failed to have an observable effect on established arthritis. IgG isotype autoantibody levels were found to be decreased in the sera of DHEA-treated mice.Conclusion. Administration of exogenous DHEA offered protection against the development of CIA. These data support the results of human studies in which low DHEA levels have been identified as a potential risk factor for the development of rheumatoid arthritis. These findings also highlight DHEA as a potential therapy worthy of further investigation. dition in New Zealand black X New Zealand white mice (for review, see ref.

An Orally Bioavailable Synthetic Analog of an Active Dehydroepiandrosterone Metabolite Reduces Established Disease in Rodent Models of Rheumatoid Arthritis

“…Low levels of DHEA in patients with rheumatoid arthritis (RA) have been reported (Wilder, 1996;Cutolo, 2000;Kanik et al, 2000), along with suggestions that replacement therapy could provide benefit. DHEA showed benefit in animal models of RA, including the DBA mouse model of collagen-induced arthritis (CIA) (Williams et al, 1997;Kobayashi et al, 2003;Röntzsch et al, 2004). However, in carefully controlled clinical trials, DHEA treatment produced only modest benefits and unwanted side effects (Giltay et al, 1999;van Vollenhoven, 2000).…”

Participation of Endogenous Dehydroepiandrosterone and Its Sulfate in the Pathology of Collagen-Induced Arthritis in Mice

“…15,16) Moreover, Williams et al reported that administration of exogenous DHEA to DBA/1J CIA mice prevented the development of CIA. 42) Taking these findings into account, the retention of DHEA on day 28 and day 48 in CIA mice may be the result of the physiological response in protection against CIA.…”

Dehydroepiandrosterone Response to the Adrenocorticotropin Test and the Combined Dexamethasone and Corticotropin-Releasing Hormone Test in Patients with Multiple Sclerosis

“…A number of studies support the view that DHEA and DHEAS are decreased in rheumatoid arthritis and SLE [16, 17]. Therapeutic compensation of this deficit by DHEA supplementation seems to have beneficial effects in these clinical conditions as well as in related animal models [18, 19, 20]. In line with these immunological effects are reports that DHEA can also influence the regulation of the Th1/Th2 balance and has inhibitory effects on the secretion of cytokines such as IL-6 in vivo and TNF-α in vitro [21, 22].…”