Enhanced production of macrophage inflammatory protein 2 (MIP-2) by in vitro and in vivo infections with encephalomyocarditis virus and modulation of myocarditis with an antibody against MIP-2.
Interleukin-8 (IL-8) is a chemotactic cytokine for neutrophils and lymphocytes. Macrophage inflammatory protein 2 (MIP-2) is a murine counterpart of IL-8. The present study was performed to determine whether MIP-2 aggravates murine myocarditis. We examined (i) the MIP-2-producing activity of encephalomyocarditis (EMC) virus-infected cultured macrophages, (ii) serial plasma MIP-2 levels in EMC virus-induced mice by enzyme-linked immunosorbent assay, and (iii) the effects of antimouse MIP-2 monoclonal antibody (MAb) in vivo upon myocarditis. The production of MIP-2 increased in an infection dose- and time-dependent manner in virus-infected RAW 264. 7 macrophages. Five-week-old C(3)H/He mice were inoculated with EMC virus. Plasma MIP-2 levels were significantly elevated in mice on days 7 and 14 postinfection. Mice were injected subcutaneously with anti-MIP-2 MAb at 10 microg/day (group 2) or 100 microg/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 prominent in the anti-MIP-2 MAb-treated group, but not in group 2, compared to the level in the controls. MIP-2 is an important naturally occurring inflammatory cytokine in myocarditis, and anti-MIP-2 MAb treatment may prevent the inflammatory response.
Kishimoto
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The Second Department of Internal Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama 930-0152, Japan. kkishi@kuhp.kyoto-u.ac.jp
Kawamata
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Sakai
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Shinohara
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Ochiai
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D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D015153:Blotting, Western; D018188:Cardiovirus Infections / Q000378:metabolism* / Q000628:therapy; D002460:Cell Line; D054426:Chemokine CXCL2; D018925:Chemokines / Q000096:biosynthesis* / Q000097:blood; D004686:Encephalomyocarditis virus / Q000502:physiology*; D008264:Macrophages / Q000378:metabolism / Q000821:virology; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000378:metabolism* / Q000628:therapy; D011817:Rabbits
D000911:Antibodies, Monoclonal; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse