Objective: To shed light on changes in the gene expression of T helper lymphocyte (Th) subpopulation, Th1, Th2 and Th17 in autoimmune myocarditis and to gain insight into the immunological mechanisms underlying the essence of myocarditis.
Methods: An experimental Lewis rat autoimmune myocarditis model was induced by immunization with cardiac C protein and completed Freund adjuvant in double foot pads and subsequent intraperitoneal injection of pertussis toxin. Two groups of normal rats without immunological injection acted as control group. Transthoracic echocardiography was performed and subsequently hearts and spleens were obtained from EAM rats at 1 week, 2 weeks, 4 weeks, 6 weeks and 8 weeks after immunization. The pathological sections of heart samples were prepared, the inflammatory score was determined by hematoxylin and eosin stain, the fibrosis score was determined by picrosirius red stain. The ratio of Th1, Th2 and Th17 subpopulation in spleen cells were measured by flow cytometry, and enzyme linked immunoabsorption assay (ELISA) was used to determine the serum level of Th1 related cytokine interferon-gamma (IFN-gamma), Th2 related cytokine interleukin (IL)-4 and Th17 related cytokine IL-17.
Results: In EAM rats, cardiac ejection fraction remained normal until 4th week, and left ventricular end systolic diameter and left ventricular end diastolic diameter decreased. However, cardiac ejection fraction decreased obviously and left ventricular end systolic diameter and left ventricular end diastolic diameter rose until 8th week. Inflammatory score increased rapidly at 2nd week after immunization and remained peek level until 4th week and then gradually decreased at 6th and 8th week. Fibrosis score and fibrosis content increased from 4th week and maintained the peek level until 8th week. Ratio of Th1 in spleen cells of EAM rats and its related cytokine in serum, IFN-gamma, increased at 1st week, arrived at the peek level until 4th week and gradually decreased at 6th week. Ratio of Th17 and IL-17 rose from 2nd-4th week and remained until 6th to 8th week. Ratio of Th2 showed no change in the previous four weeks, ratio of IL-4 increased from 4th week, and both rose at 6th week rapidly and remained until 8th week.
Conclusions: In EAM Lewis rats, The time duration from 2nd to 4th week was inflammatory stage of myocarditis while during the period of 4th week to 8th week myocarditis develops into fibrotic stage. Imbalance of Th1/Th2 takes part in the occurrence of ventricular remodeling, cellular immunity mediated by Th1 and Th17 being preponderant at inflammatory myocarditis stage while humoral immunity mediated by Th2 and Th17 being preponderant at fibrotic carditis stage.