Absence of Effects of Cyclosporine on Myocardial Lymphocyte Subsets in Coxsackievirus B3 Myocarditis in the Aviremic Stage

• Published in: Circulation research Vol. 65; no. 4; pp. 934 - 945
• Main Authors: Kishimoto, Chiharu, Abelmann, Walter H
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD American Heart Association, Inc 01.10.1989; Lippincott
• Subjects: Animals; Antigens, Differentiation - analysis; Biological and medical sciences; Blood - microbiology; Blood Cells - immunology; Blood Cells - pathology; coxsackievirus B3; Coxsackievirus Infections; Cyclosporins - pharmacology; Enterovirus B, Human - isolation & purification; Immunomodulators; Lymphocytes - immunology; Lymphocytes - pathology; Medical sciences; Mice; Myocarditis - etiology; Myocarditis - mortality; Myocarditis - pathology; Myocardium - pathology; Organ Size; Pharmacology. Drug treatments; Animal model; Pathophysiology; Picornaviridae; Rodentia; Cardiovascular disease; Enterovirus; Virus; Myocarditis; Vertebrata; Chemotherapy; Mammalia; Treatment; Mouse; Animal; Coxsackievirus B3; Myocardium; Immunosuppressive agent; Lymphocyte; Negative therapeutic reaction
• ISSN: 0009-7330; 1524-4571
• 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 3xlO 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<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.