Therapeutic effect of anti-macrophage inflammatory protein 2 antibody on influenza virus-induced pneumonia in mice.
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 microg 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.
Sakai
S
S
Department of Japanese Oriental Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
Kawamata
H
H
Mantani
N
N
Kogure
T
T
Shimada
Y
Y
Terasawa
K
K
Sakai
T
T
Imanishi
N
N
Ochiai
H
H
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D054426:Chemokine CXCL2; D007074:Immunoglobulin G / Q000276:immunology / Q000627:therapeutic use*; D007958:Leukocyte Count; D008168:Lung / Q000473:pathology / Q000821:virology; D051379:Mice; D015846:Monokines / Q000276:immunology*; D009504:Neutrophils; D009975:Orthomyxoviridae; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000473:pathology; D011024:Pneumonia, Viral / Q000188:drug therapy* / Q000473:pathology / Q000821:virology
D054426:Chemokine CXCL2; D007074:Immunoglobulin G; D015846:Monokines