Antibodies Against Intercellular Adhesion Molecule-1 and Lymphocyte Function-Associated Antigen-1 Prevent the Progression of Experimental Autoimmune Myocarditis

Experimental autoimmune myocarditis is a serious inflammatory heart disease which is characterized by lesions of infiltrated mononuclear cells and CD4 positive T lymphocytes. We demonstrated that lymphocyte function-associated antigen-1 (LFA-1) positive cells infiltrated into the lesions of this myocarditis. To elcidate the roles of adhesion molecules in the pathogenesis of autoimmune myocarditis, intercellular adhesion molecule-1 (ICAM-1)/LFA-1 pathway was investigated using rat experimental autoimmune myocarditis. Myocarditis was induced in Lewis rats by immunization with cardiac myosin. The rats were divided into four groups： control group, anti-ICAM-1-treated group, anti-LFA-1-treated group and a combination (both antibodies-treated) group. Myocardial inflammation was depressed in each antibody treated group, especially the preventive effect was augmented in the combination group. An immunohistologic study of the rat heart in the control group revealed massive infiltrations of LFA-1 or ICAM-1 positive cells, and an enhanced expression of ICAM-1 on the endothelial cells. On the other hand, the heart in the combination therapy group showed little infiltration of ICAM-1 or LFA-1 positive cells, and ICAM-1 expression was not enhanced along the endothelial cells. These data suggest that the ICAM-1/LFA-1 pathway has a crucial role in the pathogenesis of this autoimmune myocarditis