Antigenic stimulation in T-cell cultures in cardiomyopathies: differences in cytokine profiles.
Immune-mediated mechanisms are involved in the pathogenesis of cardiomyopathies. In this study, we investigate which pattern of immune response (Th1 or Th2) lies behind these diseases by analysing the basic cytokines secreted from PHA-cultured T lymphocytes and determining what differences, if any, exist between dilated cardiomyopathy (DMC) and hypertrophic cardiomyopathy (HCM). Two groups of patients were studied: 10 patients with DCM and 10 patients with HCM. Age- and sex-matched healthy individuals were used as controls. PHA-cultured T lymphocytes in the presence or absence of different myocardial 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 hyperactivity (DTH) against the same antigenic preparation was measured by the leukocyte migration inhibitory index technique. Patients were subdivided into DTH-positive and DTH-negative and re-examined for IL-2 cytokine expression. IL-6 levels were found to increase both in the presence and in the 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 patients. IFN-gamma remained unaffected in the patient groups. Almost half of the patients exhibited anergy to the DTH reaction against MA. We conclude that, upon antigenic stimulation, the initially mounted immune response (increased IL-6) is somehow blocked/switched off in patients, resulting in an immunologic tolerance/unresponsiveness to MA (IL-2 decreased, IFN-gamma unchanged). Finally, increased IL-6 could lead to a perpetuation of immunologic injury through the release of oxygen-free radicals with a cytotoxic effect on the myocardium. We hypothesize an antigen-related, defective macrophage-Th1 cell reaction, which accounts for the differences in the IL-2 profile between the DCM and HCM groups, that might cause local immune responses to lead to immunosuppression (immune tolerance effect), thus contributing to the pathogenesis of cardiomyopathies.
Boura
P
P
2nd Dept of Internal Medicine, Aristotle University of Thessaloniki, Hippokration Hospital, Greece.
Lefkos
N
N
Boudonas
G
G
Kountouras
J
J
Zacharioudaki
E
E
Efthimiadis
A
A
Tsapas
G
G
D000328:Adult; D000368:Aged; D002311:Cardiomyopathy, Dilated / Q000276:immunology*; D002312:Cardiomyopathy, Hypertrophic / Q000276:immunology*; D002464:Cell Migration Inhibition; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000276:immunology; D010835:Phytohemagglutinins / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines; D007376:Interleukin-2; D015850:Interleukin-6; D010835:Phytohemagglutinins; D007371:Interferon-gamma