Kishimoto C, Abelmann W H
Charles A. Dana Research Institute, Boston, Massachusetts.
Circ Res. 1989 Oct;65(4):934-45. doi: 10.1161/01.res.65.4.934.
To test the therapeutic efficacy of immunosuppression with cyclosporine upon the aviremic stage of coxsackievirus B3 (CB3) myocarditis, 2-week-old BALB/c mice were inoculated with 3 x 10(2) plaque-forming units of CB3, and the effects of cyclosporine on peripheral, splenic, and myocardial lymphocyte subsets were investigated. Cyclosporine, 25 mg/kg/day, was administered subcutaneously daily on days 10-31 (experiment 1) and days 30-51 (experiment 2). Treated groups were compared with infected controls for each experiment. In experiment 1, the survival rate of the cyclosporine-treated group was low (17/25 vs. 24/25, p less than 0.05). The severity of myocardial lesions and the distribution of lymphocyte subsets in myocardium and spleen on days 15-18 did not differ between treated and control groups; on the other hand, the percentages of peripheral Thy 1.2+ (pan T) and L3T4+ (activated helper T) cells on days 15-18 were decreased in the treated group, and those of B, Lyt 1+ (helper/inducer T), and Lyt 2+ (suppressor/cytotoxic T) subsets did not differ significantly. Notably, myocardial interleukin-2 receptor (IL-2R) positive cells, through which cyclosporine is considered to act, were scarce in both groups. In experiment 2, survival rates of two groups did not differ (treated, 32/34; untreated, 34/34; p = NS). The severity of myocardial lesions and the distribution of splenic lymphocyte subsets on days 35-38 also were not different between two groups. The percentages of peripheral lymphocyte subsets (Thy 1.2+ and L3T4+) were decreased in the treated group; those of B, Lyt 1+, and Lyt 2+ subsets did not differ significantly. In experiments 1 and 2, the thymus/body weight ratio in the treated groups was smaller than in the untreated group, but the spleen/body weight ratio in the treated group did not differ from the untreated group; histologically, medullary cellular depletion was evident in the thymus, not in the spleen, of the treated groups. We conclude that cyclosporine failed to change the distribution of lymphocyte subsets in the spleen as well as in the myocardium in CB3 myocarditis although it had effects on the peripheral blood and thymus, which may account for the higher mortality in the treated groups. The absence of beneficial effects of cyclosporine upon the CB3-infected myocardium may be related to the paucity of cyclosporine-sensitive cells (IL-2R, L3T4, and Lyt 2 positive cells) in the myocardium.
为检测环孢素免疫抑制疗法对柯萨奇病毒B3（CB3）心肌炎病毒血症期的治疗效果，给2周龄的BALB/c小鼠接种3×10²个CB3空斑形成单位，并研究环孢素对外周血、脾脏及心肌淋巴细胞亚群的影响。于第10 - 31天（实验1）和第30 - 51天（实验2）每天皮下注射25mg/kg/天的环孢素。每个实验将治疗组与感染对照组进行比较。在实验1中，环孢素治疗组的存活率较低（17/25对24/25，p＜0.05）。治疗组与对照组在第15 - 18天心肌病变的严重程度以及心肌和脾脏中淋巴细胞亚群的分布无差异；另一方面，治疗组在第15 - 18天外周血Thy 1.2⁺（全T细胞）和L3T4⁺（活化辅助性T细胞）细胞的百分比降低，而B细胞、Lyt 1⁺（辅助/诱导性T细胞）和Lyt 2⁺（抑制/细胞毒性T细胞）亚群的百分比无显著差异。值得注意的是，两组中环孢素被认为起作用的心肌白细胞介素-2受体（IL-2R）阳性细胞均很少。在实验2中，两组的存活率无差异（治疗组32/34；未治疗组34/34；p =无统计学意义）。两组在第35 - 38天心肌病变的严重程度以及脾脏淋巴细胞亚群的分布也无差异。治疗组外周淋巴细胞亚群（Thy 1.2⁺和L3T4⁺）的百分比降低；B细胞、Lyt 1⁺和Lyt 2⁺亚群的百分比无显著差异。在实验1和2中，治疗组的胸腺/体重比小于未治疗组，但治疗组的脾脏/体重比与未治疗组无差异；组织学上，治疗组的胸腺髓质细胞减少明显，脾脏则无。我们得出结论，环孢素未能改变CB3心肌炎脾脏及心肌中淋巴细胞亚群的分布，尽管它对外周血和胸腺有影响，这可能是治疗组死亡率较高的原因。环孢素对感染CB3的心肌无有益作用可能与心肌中环孢素敏感细胞（IL-2R、L3T4和Lyt 2阳性细胞）缺乏有关。
