Effect of cyclophosphamide on lymphokine production in MRL/lpr.Yaa mice.
The Y chromosome (Yaa gene) from autoimmune BXSB mice has been shown to be responsible for the acceleration of autoimmune symptoms when transferred to MRL/lpr mice. We examined the pathological, serological and immunological characteristics of MRL/lpr. Yaa mice and the suppressive effect of cyclophosphamide (CP) on the mice. MRL/lpr. Yaa mice spontaneously developed a massive lymphadenopathy characterized by hypergammaglobulinemia, the presence of several autoantibodies, and autoimmune disease. In MRL/lpr. Yaa mice, IL-2, IL-4 and IL-5 production in concanavalin A (Con A)-stimulated splenocytes were about 10-fold lower than in BALB/c mice at 5 weeks of age. The concentrations of these lymphokines remained low until the mice were 16 weeks of age. The production of IFN-gamma and IL-6 in 16 week old MRL/lpr. Yaa mice was about 4- and 2-fold lower, respectively, though these levels were similar in both strains at 8 weeks of age. It was found that this dysregulation of T cell function was almost identical to that in MRL/lpr mice. Administration of CP to MRL/lpr. Yaa mice ameliorated nephritis, and suppressed production of autoantibodies and the accumulation of abnormal T cells. CP also significantly elevated the production of lymphokines. These findings suggest that an abnormality of T cell function may contribute to the autoimmune pathogenesis of MRL/lpr. Yaa mice and that CP probably ameliorates auto-immune disease by improving the T cell functions.
Kamada
H
H
Department of Pharmacology, Gifu Pharmaceutical University, Japan.
Takaoka
Y
Y
Kitagaki
K
K
Nagai
H
H
D000818:Animals; D001323:Autoantibodies / Q000096:biosynthesis; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology*; D003520:Cyclophosphamide / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005921:Glomerulonephritis / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008222:Lymphokines / Q000096:biosynthesis*; D008232:Lymphoproliferative Disorders / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C
D001323:Autoantibodies; D007166:Immunosuppressive Agents; D008222:Lymphokines; D003520:Cyclophosphamide