Kirtland H H, Mohler D N, Horwitz D A
N Engl J Med. 1980 Apr 10;302(15):825-32. doi: 10.1056/NEJM198004103021502.
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.
为了验证甲基多巴通过抑制抑制性淋巴细胞的活性诱导红细胞自身抗体这一假说，我们研究了其对多种免疫功能的影响。甲基多巴抑制了由商陆有丝分裂原刺激的外周血单核细胞对IgG产生的T淋巴细胞抑制作用。这种效应发生在用甲基多巴孵育的分离T细胞以及从服用甲基多巴的患者体内获取的T细胞中。此外，该药物使外周血单核细胞在体外对有丝分裂原的增殖反应降低了30%至80%，且这种降低主要涉及T淋巴细胞的激活。甲基多巴在体外和体内还导致淋巴细胞内的环磷酸腺苷持续升高。我们推测，甲基多巴通过使淋巴细胞内的环磷酸腺苷持续增加来改变免疫系统，这抑制了抑制性T细胞的功能。这些效应可能导致一些患者的B细胞产生不受调控的自身抗体。
