Effects of granulocyte colony-stimulating factor upon coxsackievirus B3 myocarditis in mice

Abstract

Granulocyte colony-stimulating factor is a potent activator of mature granulocytes, and subsequently enhances superoxide release. The purpose of this study was to investigate the effects of granulocyte colony-stimulating factor upon murine coxsackievirus B3 myocarditis in relation to free radical-mediated cardiac damage. Two-week-old, male, C3H/He mice were inoculated intraperitoneally with coxsackievirus B3. Granulocyte colony-stimulating factor 20 micrograms.kg-1.day-1, polyethylene glycol-conjugated superoxide dismutase (an enzyme catalyzing the conversion of O2- to H2(O2)) 1 x 10(3) U.kg-1.day-1 and granulocyte colony-stimulating factor 20 micrograms.kg-1.day-1, plus polyethylene glycol-conjugated superoxide dismutase 1 x 10(3) U. kg-1. day-1, were injected subcutaneously daily on days 0 to 14. Treated groups were compared to the infected, untreated group. The survival rate in the polyethylene glycol-conjugated superoxide dismutase group was higher than that of the untreated group on day 14, but on day 7, cardiac pathology was not significantly different among the four groups. On day 14, the scores of cellular infiltration, myocardial necrosis and calcification were lower in the polyethylene glycol-conjugated superoxide dismutase group and in the granulocyte colony-stimulating factor plus polyethylene glycol-conjugated superoxide dismutase group than in the untreated group. The myocardial virus titres on days 7 and 14 did not differ significantly among the four groups. The number of total white blood cell and neutrophil counts were significantly greater in the granulocyte colony-stimulating factor group than in the untreated group on day 7. Taken altogether with the previous reports and present evidence that the administration of granulocyte colony-stimulating factor did not exacerbate coxsackievirus B3 myocarditis, it may be that oxygen-free radicals appeared to be derived not from leukocytes but from other components in this experimental model of myocarditis, whereas the myocardium was inflamed with leukocytes.