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.