Enhanced production of macrophage inflammatory protein 2 (MIP-2) by in vitro and in vivo infections with encephalomyocarditis virus and modulation ofmyocarditis with an antibody against MIP-2

Interleukin-8 (IL-8) is a chemotactic cytokine for neutrophils and lymphocy tes, Macrophage inflammatory protein 2 (MIP-2) is a murine counterpart of I L-8. The present study was performed to determine whether MIP-2 aggravates murine myocarditis. We examined (i) the MIP-2-producing activity of encepha lomyocarditis (EMC) virus-infected cultured macrophages, (ii) serial plasma MIP-2 levels in EMC virus-induced mice by enzyme-linked immunosorbent assa y, and (iii) the effects of antimouse MIP-2 monoclonal antibody (MAb) in vi ce upon myocarditis. The production of MIP-2 increased in an infection dose - and time-dependent manner in virus-infected RAW 264.7 macrophages. Five-w eek-old C3H/He mice were inoculated with EMC virus, Plasma MIP-2 levels wer e significantly elevated in mice on days 7 and 11 postinfection. Mice were injected subcutaneously with anti-MIP-2 MAb at 10 mug/day (group 2) or 100 mug/day (group 3) on days 0 to 5 and were observed until day 21. Uninfected control mice (group 1) were prepared. The survival rate was higher in the anti-MIP-2-treated group (group 3), but not in group 2, than in the control group. Histopathological analysis revealed that cellular infiltration and myocardial necrosis with macrophage and T-cell accumulation were less promi nent in the anti-MIP-2 MAb-treated group, but not in group 2, compared to t he level in the controls, MIP-2 is an important naturally occurring inflamm atory cytokine in myocarditis, and anti-MIP-2 MAb treatment may prevent the inflammatory response.