Role of MIP-2 in coxsackievirus B3 myocarditis.
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 the role of MIP-2 in murine myocarditis. We examined (1) the MIP-2 producing activity of Coxsackievirus B3 (CB3)-infected cultured macrophages, (2) serial plasma MIP-2 levels in CB3-induced mice by enzyme-linked immunosorbent assay (ELISA), and (3) the effects of anti-mouse 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. Three-week-old C(3)H/He mice were inoculated with CB3. Plasma MIP-2 levels were significantly elevated in mice on days 7, 10 and 14 post-infection. Mice were injected subcutaneously with anti-MIP-2 mAb at 10 microg/day (Group 2) or 100 microg/day (Group 3) on days 0-7, and were observed until day 14. Uninfected control mice (Group 1) were injected with saline. 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 groups as compared to the controls. MIP-2 is an important naturally occurring inflammatory cytokine in CB3 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, 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 / Q000008:administration & dosage / Q000276:immunology; D002460:Cell Line; D054426:Chemokine CXCL2; D018925:Chemokines / Q000276:immunology* / Q000378:metabolism; D002522:Chlorocebus aethiops; D003384:Coxsackievirus Infections / Q000276:immunology*; D029822:Enterovirus B, Human / Q000276:immunology* / Q000502:physiology; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D009205:Myocarditis / Q000276:immunology / Q000821:virology*; D011817:Rabbits; D014709:Vero Cells
D000911:Antibodies, Monoclonal; D054426:Chemokine CXCL2; D018925:Chemokines; C404915:Cxcl2 protein, mouse