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

Granulocyte colony-stimulating factor is a potent activatorof mature granulocytes, and subsequently enhances superoxiderelease. The purpose of this study was to investigate the effectsof granulocyte colony-stimulating factor upon murine coxsackievirusB3 myocarditis in relation to free radical-mediated cardiacdamage. Two-week-old, male, C₃H/He mice were inoculated intraperitoneallywith coxsackievirus B3. Gramulocyte colony-stimulating factor20 µg.kg^–1. day^–1, polyethylene glycol-conjugatedsuperoxide dismutase (an enzyme catalyzing the conversion ofO₂^- to H₂O₂) 1 x 10³ U.kg^–1 day^–1 and granulocytecolony-stimulating factor 20 µg. kg^–1 day^–1,plus polyethylene glycol-conjugated superoxide dismutase 1 x10³ U.kg^–1. day^–1, were injected subcutaneouslydaily on days 0 to 14. Treated groups were compared to the infected,untreated group. The survival rate in the polyethylene glycol-conjugatedsuperoxide dismutase group was higher than that of the untreatedgroup on day 14, but on day 7, cardiac pathology was not significantlydifferent among the four groups. On day 14, the scores of cellularinfiltration, myocardial necrosis and calc were lower in thepolyethylene glycol-conjugated superoxide disnuitase group andin the granulocyte colony-stimulating factor plus polyethyleneglycol-conjugated superoxide dismutase group than in the untreatedgroup. The myocardial virus titres on days 7 and 14 did notd sign y among the four groups. The number of total white bloodcell and neutrophil counts were signifIcantly greater in thegranulo cyte colony-stimulating factor group than in the untreatedgroup on day 7. Taken altogether with the previous reports andpresent evidence that the administration of granulocyte colony-stimulatingfactor did not exacerbate coxsackievirus B3 myocarditis, itmay be that oxygen-free radicals appeared to be derived notfrom leukocytes but from other components in this experimentalmodel of myocarditis, whereas the myocardium was inflamed withleukocytes.