Antigenic stimulation in T-cell cultures in cardiomyopathies: differences in cytokine profiles

Immune-mediated mechanisms are involved in the pathogenesis of cardiomyopat hies. In this study, we investigate which pattern of immune response (Th-1 or Th-2) lies behind these diseases by analysing the basic cytokines secret ed from PHA-cultured T lymphocytes and determining what differences, if any , exist between dilated cardiomyopathy (DMC) and hypertrophic cardiomyopath y (HCM). Two groups of patients were studied: 10 patients with DCM and 10 p atients with HCM. Age- and sex-matched healthy individuals were used as con trols. PHA-cultured T lymphocytes in the presence or absence of different m yocardial antigen (MA) concentrations were measured. Interleukine-2 (IL-2), Interleukine-6 (IL-6) and Interferon-gamma (IFN-gamma levels were measured in culture supernatants by an ELISA method. At the same time, delayed-type hypereactivity (DTH) against the same antigenic preparation was measured b y the leukocyte migration inhibitory index technique. Patients were subdivi ded into DTH-positive and DTH-negative and re-examined for IL-2 cytokine ex pression. IL-6 levels were found to increase both in the presence and in th e absence of MA in the patient groups compared to the controls. IL-2 levels were decreased in both groups, in an antigen dose-related manner. Anergic patients showed a further reduction in IL-2 levels for both groups of patie nts. IFN-gamma remained unaffected in the patient groups. Almost half of th e patients exhibited energy to the DTH reaction against MA. We conclude tha t, upon antigenic stimulation, the initially mounted immune response (incre ased IL-6) is somehow blocked/switched off in patients, resulting in an imm unologic tolerance/unresponsiveness to MA (IL-2 decreased, IFN-gamma unchan ged). Finally, increased IL-6 could lead to a perpetuation of immunologic i njury through the release of oxygen-free radicals with a cytotoxic effect o n the myocardium. We hypothesize an antigen-related, defective macrophage-T h-1 cell reaction, which accounts for the differences in the IL-2 profile b etween the DCM and HCM groups, that might cause local immune responses to l ead to immunosuppression (immune tolerance effect), thus contributing to th e pathogenesis of cardiomyopathies.