Involvement of thymus in amiodarone-treated autoimmune myocarditis in rats

We previously showed that amiodarone, an iodine-rich benzofuranic derivative, interferes with the progression of myocarditis using a rat model of experimental autoimmune myocarditis. Further studies have also revealed that intraperitoneal treatment with 12.5 mg/kg amiodarone, which is below the range of its therapeutic plasma concentration, also effectively interferes with the progression of myocarditis using the same model. The relationship between myocarditis and the thymus has not been studied in either patients or animal models. To investigate whether the thymus is involved in the effect of amiodarone on experimental autoimmune myocarditis, we examined its phenotypic distribution in thymocytes and peripheral blood lymphocytes using flow cytometry. We found no significant differences in the proportions of CD4+ and CD8+ T cells and the CD4+/CD8+ T cell ratio in the control group compared with amiodarone-treated group. However, amiodarone-treated group induced a decrease in the proportion of CD4+TNF+ and CD4+IL-4+ T cells and an increase in CD4+IFN+ T cells, resulting in a significant reduction of the CD4+TNF+/CD4+IFN+ and CD4+IL-4+/CD4+IFN+ T cell ratios. These results suggest for the first time that the thymus is actively involved when myocarditis is treated with amiodarone.