Mycophenolate mofetil ameliorates perivascular T lymphocyte inflammation and reduces the double-negative T cell population in SLE-prone MRLlpr/lpr mice.
Effects on T lymphocyte mediated pathology, phenotypes, and functions in MRLlpr/lpr mice given mycophenolate mofetil (MMF) (100 mg/kg/day) via drinking water or controls given ip cyclophosphamide (CYC) injections (1.8 mg/mouse/week) or water were described. Both MMF and CYC treatment diminished kidney and large salivary gland perivascular cell infiltrates, reduced profoundly double-negative (DN) T cell frequencies, decreased total lymphocyte number in spleen, and increased in vitro proliferative response to Con A. IFN-gamma and IL-10 in supernatants from Con A stimulated spleen cells were augmented after MMF but not CYC treatment. MMF treatment increased whereas CYC reduced IL-12 in serum. Kidney expressions of IFN-gamma, IL-10, and IL-12 mRNA were unaffected by MMF but decreased by CYC. Our results demonstrate that MMF and CYC suppress perivascular T lymphocyte inflammation by reducing the DN T cell population and by amelioration of T cell function. The varying cytokine patterns suggest different mechanisms of the two drugs.
Jonsson
C A
CA
Department of Rheumatology, University of Göteborg, Göteborg, S-413 46, Sweden. charlotte.jonsson@immuno.gu.se
Erlandsson
M
M
Svensson
L
L
Mölne
J
J
Carlsten
H
H
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D002452:Cell Count; D002455:Cell Division; D003208:Concanavalin A / Q000494:pharmacology; D003520:Cyclophosphamide / Q000494:pharmacology; D016207:Cytokines / Q000097:blood / Q000235:genetics; D004195:Disease Models, Animal; D005260:Female; D006968:Hypersensitivity, Delayed; D016130:Immunophenotyping; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000166:cytology / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology*; D008297:Male; D051379:Mice; D019463:Mice, Inbred MRL lpr; D009173:Mycophenolic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger; D012469:Salivary Glands / Q000098:blood supply / Q000166:cytology; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D014657:Vasculitis / Q000473:pathology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D016207:Cytokines; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D003208:Concanavalin A; D003520:Cyclophosphamide; D009173:Mycophenolic Acid