In the present study, the mechanisms and importance of the Fc portion of
immunoglobulin in experimental giant cell
myocarditis were examined. Giant cell
myocarditis was induced in rats by immunization of porcine
cardiac myosin. Human intact
immunoglobulin (1 g. kg(-1). d(-1)) or F(ab')(2) fragments of human
immunoglobulin (1 g. kg(-1). d(-1)) were administered intraperitoneally daily on days 1 to 21. Intact
immunoglobulin administration significantly ameliorated
myocarditis, but F(ab')(2) fragments did not. The
ribonuclease protection assay revealed that
therapy with intact
immunoglobulin, but not F(ab')(2) fragments, suppressed the
mRNA expressions of inflammatory and proinflammatory
cytokines. Immunohistochemical analysis showed that
therapy with intact
immunoglobulin, but not F(ab')(2) fragments, suppressed dendritic cell (DC) expression during both the early and the subsequent fulminant phases. Moreover, the early treatment of intact
immunoglobulin until the 11th day or 14th day, when the expression of DCs was completely suppressed, ameliorated
myocarditis. However, the late treatment of intact
immunoglobulin beginning on day 15, when the expression of DCs had already been completed, failed to ameliorate the condition. An in vitro study showed that intact
immunoglobulin, but not F(ab')(2) fragments, suppressed the
lipopolysaccharide-induced
interleukin-1beta production associated with the downregulation of CD32
antigen (Fcgamma receptor II) expression. Thus, intact immunoglobulin therapy markedly suppressed
myocarditis as a result of
Fc receptor-mediated anti-inflammatory action, and the suppression of the disease was associated with the suppression of DCs, ie, the suppression of the initial
antigen-priming process in experimental giant cell
myocarditis.