Effects of lobenzarit on murine acute viral myocarditis

Abstract

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 less than 0.05; heart: 30.1 +/- 4.6% vs. 15.8 +/- 4.3%, p less than 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 less than 0.05). Thus, these findings suggest that CCA may aggravate EMC-induced acute myocarditis by enhancing the number of Lyt2+ cells.

The effects of lobenzarit disodium, a novel immunomodulator, upon murine coxsackievirus B3 myocarditis

“…A recent study reported that CCA blocked HLA-DR antigen expression on endothelial cells [23]. To our knowledge, however, there is only one reported study of the effects of CCA upon acute myocarditis [13], where immune or autoimmune mechanisms are thought to be involved in the pathogenesis [1,2].…”

“…Recent studies of T-cell activation disclosed that the signal transduction pathway is set in motion by multiple activating signals. As for the field of myocarditis, Yokoyama et al reported that CCA increased the peripheral Ly2 population (CDS) in encephalomyocarditis virus murine acute myocarditis, and enhanced myocardial damage [13]. The difference between these two viruses regarding the number of T-cell subsets in virus-infected drug-treated mice is unknown.…”

“…The dosage of CCA was 2.5 mg/kg per day. This dose was based on those of previous reports [13,16,17].…”

“…Lobenzarit disodium (CCA: disodium 4-chloro-2, 2'-iminodibenzoate) is a newly developed immunomodulating drug, which may affect T lymphocyte function [13]. Abnormal behavior of the immune system has been demonstrated as a pathogenetic mechanism of CB3 myocarditis [14,15].…”

An Approach to the Treatment of Pediatric Myocarditis

“…[55] In a similar model, lobenzarit, a disodium immunomodulatory drug known to enhance suppressor T cell activity, was shown to increase both T cell response to, and the severity of myocarditis induced by, ECMV. [56] However, when used to treat mice infected with Coxsackie virus B3, lobenzarit mitigated the immune response to viral infection. [57] Despite encouraging data with these agents specific to lymphocyte immunosuppression, attempts to use more general immunosuppressant agents, such as cyclosporine and prednisolone, have been shown to enhance mortality in mice infected with ECMV.…”