Methyldopa inhibition of suppressor-lymphocyte function: a proposed cause of autoimmune hemolytic anemia.
To test the hypothesis that methyldopa induces red-cell autoantibodies by inhibiting the activity of suppressor lymphocytes, we studied its effect on several immune functions. Methyldopa inhibited T-lymphocyte suppression of IgG production by peripheral-blood mononuclear cells stimulated by poke-weed mitogens. This effect occurred in isolated T cells incubated with methyldopa and in T cells obtained from patients taking methyldopa. In addition, the drug caused a 30 to 80 per cent reduction in the proliferative response of peripheral-blood mononuclear cells to mitogens in vitro, and this reduction primarily involved the activation of T lymphocytes. Methyldopa also caused a persistent elevation of intracellular lymphocyte cyclic AMP in vitro and in vivo. We postulate that methyldopa alters the immune system by causing a persistent increase in lymphocyte cyclic AMP, which inhibits suppressor T-cell function. These effects may lead to unregulated autoantibody production by B cells in some patients.
D000744:Anemia, Hemolytic, Autoimmune / Q000139:chemically induced* / Q000276:immunology; D001323:Autoantibodies / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology; D000242:Cyclic AMP / Q000097:blood; D004912:Erythrocytes / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D066298:In Vitro Techniques; D008213:Lymphocyte Activation / Q000187:drug effects; D008750:Methyldopa / Q000494:pharmacology*; D050378:T-Lymphocytes, Regulatory / Q000032:analysis / Q000187:drug effects* / Q000276:immunology
D001323:Autoantibodies; D007074:Immunoglobulin G; D008750:Methyldopa; D000242:Cyclic AMP