The effect of intravenous immunoglobulins on the progression of experimental autoimmune myocarditis in the rat.
The aim of this study was to evaluate the efficacy of two experimental regimes of human intravenous immunoglobulins (IVIG) on the progression of experimental autoimmune myocarditis (EAM). EAM is induced by immunization against myosin and represents a T-cell-dependent disorder that progresses toward dilated cardiomyopathy similar to the human equivalent. No effective treatment is currently at hand for management of the disorder, as immunosuppressant drugs are associated with multiple side effects. Three groups of Lewis rats were induced to develop EAM by immunization with porcine myosin and sacrificed 21 days later. Group A received a 5-day regimen of IVIG (800 mg/kg) following induction of the disorder; Group B received a daily dose of IVIG (800 mg/kg) and group C was treated with PBS. IVIG given daily but not during the first 5 days significantly suppressed myocarditis score (0.81 +/- 0.26 and 1.14 +/- 0.42, respectively) in comparison with controls (mean score of 1.78 +/- 0.36). The effect was accompanied by a reduction in the cellular and humoral immune response of the respective animals toward myosin. IVIG was deposited within the extracellular matrix surrounding the damaged myocytes. TNF-alpha expression was reduced in both groups treated with IVIG, whereas iNOS expression paralleled the extent of myocardial inflammation regardless of treatment. IVIG at doses twice those applied for human disease are effective in ameliorating the progression of EAM. The effect may be mediated by suppression of the cellular and humoral response to myosin. IVIG may be found clinically feasible in humans as an adjuvant or single therapy for autoimmune myocarditis.
George
J
J
Department of Cardiology and Cardiovascular Research Laboratory, Tel-Aviv Medical Center, Tel-Aviv, Israel.
Barshack
I
I
Malka
E
E
Goldberg
I
I
Keren
P
P
Laniado
S
S
Keren
G
G
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D004195:Disease Models, Animal; D018450:Disease Progression; D019084:Fluorescent Antibody Technique, Indirect; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000032:analysis / Q000493:pharmacokinetics / Q000494:pharmacology*; D008297:Male; D009205:Myocarditis / Q000276:immunology* / Q000473:pathology; D009206:Myocardium / Q000276:immunology* / Q000473:pathology*; D009218:Myosins / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew
D016756:Immunoglobulins, Intravenous; D009218:Myosins