FOR NEW METHOD TO MAKE A DIAGNOSIS OF AUTOIMMUNE CARDIOMYOPATHY

通过β-肾上腺素能受体的G蛋白不仅是心肌收缩的调节剂，也是免疫反应的调节剂。因此，我们首先研究了抑制性G(Gi)蛋白对心肌炎症的免疫调节作用。将肌球蛋白免疫的Lewis大鼠(EAM：实验性自身免疫性心肌炎/心肌病)分为两组：一组在免疫的同时注射具有代表性的胃肠道蛋白抑制剂百日咳毒素(PTX)(诱导期)，另一组在免疫后注射(效应期)。评价PTX对EAM的辅助作用。随着诱导期的使用，PTX使EAM恶化。另一方面，在效应期使用时，PTX改善了其病情严重程度。这种双向G蛋白信号可能是自身免疫性心肌病的主要免疫调节途径之一。另一方面，促红细胞生成素(EPO)对心肌损伤具有保护作用。因此，第二，我们研究了EPO对心肌炎症的免疫调节作用。EAM大鼠每天服用两种EPO中的任何一种。EPO可明显减轻EAM的严重程度，降低心肌组织中干扰素-γ/肌钙蛋白T和IL-10/TNTm RNA的表达。虽然EPO在体外不能抑制肌球蛋白特异的、致心肌梗死的T细胞的增殖，但通过静脉转移这些T细胞产生的EAM可以通过每天给予EPO而得到改善。EPO在效应期具有抗炎作用，为了建立诊断人类自身免疫性心肌炎的新方法，考虑了上述两点：作为β刺激的GI蛋白信号和作为内源性体液因子的促红细胞生成素。

The G protein through β-adrenergic receptors has been focused on as a modulator of not only myocardial contractility but also immune response. Thus, firstly, the immunomodulatory effects of the inhibitory G (Gi) protein on myocardial inflammation are studied. Myosin-immunized Lewis rats (EAM : experimental autoimmune myocarditis/cardiomyopathy) were divided into two groups : administered with pertussis toxin (PTX), a representative Gi protein inhibitor, simultaneously with immunization (in induction phase) and the other administered after immunization (in effector phase). They were evaluated adjunctive effect of PTX on EAM. With the use in induction phase, PTX deteriorated EAM. On the other hand, in the use in effector phase, PTX improved its disease severity. This bidirectional G protein signal must be one of the major immunomodulating pathways in autoimmune cardiomyopathy.On the other hand, erythropoietin (EPO) has a protective effect on myocardial damage. Thus, secondly, immunomodulatory effects of EPO on myocardial inflammation were investigated. EAM rats were treated daily with either EPO. EPO markedly reduced severity in EAM with the reduction of IFN-gamma/troponin T and IL-10/TNTmRNA in the myocardium. Although EPO did not suppress the proliferation of myosin-specific, myocarditogenic T cells in vitro, EAM produced by intravenous transfer of those T cells were ameliorated by daily administration of EPO. EPO has anti-inflammatory effect on the effecter phase.For establishment of new method to make a diagnosis of autoimmune myocarditis in human being, the above mentioned two points are taken into account : Gi protein signal as beta-stimulation and erythropoietin as an intrinsic humoral factor.