Summary
Lobenzarit (CCA) is a newly developed immunomodulating drug that has been demonstrated to enhance suppressor T-cell number and function. In this study we investigated the effect of CCA on murine myocarditis induced by the encephalomyocarditis (EMC) virus. Mice were first inoculated with the EMC virus. CCA (100 mg/kg) was administered daily for 14 days, starting on the day the mice were inoculated. The concentrations of Lyt2+ (suppressor/cytotoxic T) cells in the peripheral blood and heart were examined by laser flow cytometry and in situ staining. The concentration of Lyt2+ cells increased significantly in the peripheral blood and heart of CCA-treated mice when compared with untreated mice (blood: 23.0±2.6% vs. 18.8±2.8%, p<0.05; heart: 30.1±4.6% vs. 15.8±4.3%, p<0.05, respectively). Surprisingly, however, the severity of myocardial inflammation in CCA-treated mice was significantly greater than in untreated mice (area of inflammation: 33.1±10.5% vs. 18.8 ±19.5%, respectively, p<0.05). Thus, these findings suggest that CCA may aggravate EMC-induced acute myocarditis by enhancing the number of Lyt2+ cells.
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References
Eckstein R, Mempel W, Bolte HD. Reduced suppressor cell activity in congestive cardiomyopathy and myocarditis. Circulation 1992;65:1224–1229.
Koga Y, Miyazaki Y, Toshima H, et al. Lymphocyte subsets in patients with acute myopericarditis, arrhythmias and dilated cardiomyopathy. Jpn Circ J 1989;53:78–86.
Shiokawa Y, Horiuchi Y, Mizushima Y, et al. A multicenter double-blind controlled study of lobenzarit, a novel immunomodulator, in rheumatoid arthritis. J Rheumatol 1984;11: 615–623.
Nakano T, Yamashita Y, Ohsugi Y, et al. The effect of CCA (lobenzarit disodium) on suppressor T cell function and the production of autoantibodies in New Zealand Black and New Zealand White F1 mice. Immunopharmacology 1985;5: 293–302.
Itoh K, Kurane I, Saito F, et al. Regulatory effect of CCA on immune responses. Clin Immunol 1983;15:242–252 (in Japanese).
Ohsugi Y, Nakano T, Hata S, et al. N-(2-carboxyphenyl)-4-chloroanthranilic acid disodium salt: A novel anti-arthritic agent without anti-inflammatory and immunosuppressive activities. J Pharm Pharmac 1977;29:636–637.
Adamson TC, Frisman DM, Howell FV. Immunohistologic analysis of lymphoid infiltrates in primary Sjogren's syndrome using monoclonal antibodies. J Immunol 1983;130: 203–208.
Kishimoto C, Kuribayashi K, Fukuma K, et al. Immunologic identification of lymphocyte subsets in experimental murine myocarditis with encephalomyocarditis virus: Different kinetics of lymphocyte subsets between the heart and the peripheral blood, and significance of Thy1.2+ (pan T) and Lyt1+,23+ (immature T) subsets in the development of myocarditis. Circ Res 1987;61:715–725.
Huber SA, Lodge PA. Coxsackievirus B-3 myocarditis in Balb/c mice: Evidence for autoimmunity to myocyte antigens. Am J Pathol 1984;116:21–29.
Gutherie M, Lodge PA, Huber SA. Cardiac injury in coxsackievirus group B, type 3 induced myocarditis in Balb/c mice is mediated by Lyt2+ cytolytic lymphocytes. Cell Immunol 1984;88:558–567.
Houten VN, Huber SA. Role of cytotoxic T cells in experimental myocarditis. Springer Semin Immunopathol 1989; 11:61–68.
Blay R, Simpson K, Leslie K, et al. Coxsackievirus-induced disease CD4+ cells initiate both myocarditis and pancreatitis in DBA/2 mice. Am J Pathol 1989;135:899–907.
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Yokoyama, T., Kanda, T., Suzuki, T. et al. Effects of lobenzarit on murine acute viral myocarditis. Cardiovasc Drug Ther 6, 403–407 (1992). https://doi.org/10.1007/BF00054189
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DOI: https://doi.org/10.1007/BF00054189