We investigated the effect of anti-macrophage inflammatory protein 2 immunoglobulin G (aMIP-2 IgG) on the progression of influenza virus-induced pneumonia in mice. When mice were infected with a mouse lung-adapted strain of influenza A/PR/8/34 virus by intranasal inoculation, neutrophil counts in the bronchoalveolar lavage fluid (BALF) increased in parallel with the kinetics of MIP-2 production, which peaked 2 days after infection. After intracutaneous injection of a dose of 10 or 100 g of aMIP-2 IgG once a day on days 0 and 1, neutrophil counts in BALF on day 2 were reduced to 49 or 37%, respectively, of the value in the control infected mice administered anti-protein A IgG. The antibody administration also improved lung pathology without affecting virus replication. Furthermore, by prolonged administration with a higher or lower dose for up to 5 days, body weight loss became slower and finally 40% of mice in both treatment groups survived potentially lethal pneumonia. These findings suggest that MIP-2-mediated neutrophil infiltration during the early phase of infection might play an important role in lung pathology. Thus, MIP-2 was considered to be a novel target for intervention therapy in potentially lethal influenza virus pneumonia in mice.

WE in ves tigate d th e effect of ferulic acid (FA) and is oferulic acid (IFA),

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We investigated whether (+)-catechin, a building block of tannins contained in the extract of Ephedrae herba (EHext), exerts an inhibitory effect on the acidification of intracellular compartments such as endosomes and lysosomes (referred to as ELS), and thereby inhibits the growth of influenza A PR/8/34 (PR8) virus (H1N1 subtype) in Madin-Darby canine kidney cells. The vital fluorescence microscopic study with acridine orange showed that 1-h treatment with (+)-catechin inhibited the acidification of ELS in a concentration-dependent manner (1.0-10.0 mM). Moreover, the growth of PR8 virus was inhibited markedly when the cells were treated with (+)-catechin (1.25-10.0 mM) for 1 h immediately after infection, or treated within as little as 5 to 10 min after infection. Conversely, virus growth resumed within 3 h concomitantly with the reappearance of acidified ELS after removal of (+)-catechin. Similar to EHext, (+)-catechin inhibited both the acidification of ELS and the influenza virus growth. It suggests that (+)-catechin is one of the active components in EHext.

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 g/day (group 2) or 100 g/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.