Auranofin-induced suppression of autoimmune antibody production and inflammation in genetically autoimmune-prone mice.
The gold compound auranofin and lobenzarit (CCA) were compared in regard to effects on development of an autoimmune-like disease in MRL/1 mice, which normally develop elevated levels of serum anti-DNA antibodies and rheumatoid factor as well as joint lesions similar to those seen in patients with rheumatoid arthritis. MRL/1 mice, which are genetically prone to development of autoimmune disease, were given auranofin or lobenzarit by gavage for 15 weeks, starting at 6 weeks of age. Mice were examined periodically for immunological abnormalities as well as histologic changes in articular joints. The auranofin-treated mice showed marked diminution in development of anti-DNA antibodies and serum rheumatoid factor as compared to control animals. Although higher than in the auranofin-treated animals, CCA-treated mice also had lower levels of serum autoantibodies than those seen in the control animals. Examination of limb joints for histopathologic changes indicated that the auranofin-treated animals developed only the slightest evidence of lesions as compared to control animals. CCA-treated mice also had a lessening of lesion development compared to control animals, but lesions were more developed than in auranofin-treated mice. This study indicates that auranofin is more effective than CCA in diminishing development of autoimmunity in MRL/1 mice.
Friedman
H
H
Department of Medical Microbiology and Immunology, University of South Florida College of Medicine, Tampa.
Specter
S
S
Klein
T
T
Newton
C
C
Rivenbark
M
M
Rowlands
D
D
Walz
D T
DT
D000284:Administration, Oral; D000818:Animals; D000906:Antibodies / Q000276:immunology; D000888:Antibodies, Anti-Idiotypic / Q000276:immunology; D000917:Antibody Formation / Q000187:drug effects; D001310:Auranofin / Q000008:administration & dosage / Q000494:pharmacology*; D001327:Autoimmune Diseases / Q000276:immunology / Q000473:pathology; D015551:Autoimmunity / Q000187:drug effects; D004247:DNA / Q000276:immunology; D007074:Immunoglobulin G / Q000096:biosynthesis / Q000276:immunology; D007075:Immunoglobulin M / Q000096:biosynthesis; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000494:pharmacology; D007249:Inflammation / Q000276:immunology*; D007592:Joint Diseases / Q000276:immunology; D008297:Male; D051379:Mice; D062367:ortho-Aminobenzoates / Q000008:administration & dosage / Q000494:pharmacology
D000906:Antibodies; D000888:Antibodies, Anti-Idiotypic; D007074:Immunoglobulin G; D007075:Immunoglobulin M; D007166:Immunosuppressive Agents; C048844:anti-IgG; D062367:ortho-Aminobenzoates; D001310:Auranofin; D004247:DNA; C015735:lobenzarit