Modulation of macrophage-lymphocyte interactions by the antiarthritic gold compound, auranofin.
Auranofin (AF), a new oral gold agent effective for treating rheumatoid arthritis (RA) was evaluated for its ability to alter macrophage and lymphocyte functions of immune mediated chronic inflammation. AF (2 microM) inhibited antigen presentation by splenic macrophages to sensitized (DNFB) lymph node cells in vitro and also inhibited production of IL-2 and IL-1 by lymphocytes and macrophages, respectively. When AF suppressed Con-A induced mitogenesis in vitro, there were no inhibitory effects on Con-A induced suppressor T cell functions. AF administered orally to normal mice did not affect antigen presentation. DNFB contact sensitivity or Con-A induced mitogenesis. High concentrations of topical AF inhibited local immune responses to contact sensitizing agents and enhanced the induction of antigen specific suppressor T cells. Optimally, in vitro or in vivo AF inhibited macrophage and helper T cell functions with impairing the induction of suppressor T cells. After chronic treatment, similar effects could contribute to the efficacy of AF in humans with RA.
Griswold
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Lee
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JC
Poste
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Hanna
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D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects; D001310:Auranofin; D006051:Aurothioglucose / Q000031:analogs & derivatives* / Q000494:pharmacology; D002450:Cell Communication / Q000187:drug effects; D006046:Gold / Q000031:analogs & derivatives*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects; D008214:Lymphocytes / Q000187:drug effects* / Q000276:immunology; D008264:Macrophages / Q000187:drug effects* / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects
D007375:Interleukin-1; D007376:Interleukin-2; D006051:Aurothioglucose; D001310:Auranofin; D006046:Gold