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Journal of Virology, March 2000, p. 2472-2476, Vol. 74, No. 5
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Therapeutic Effect of Anti-Macrophage Inflammatory Protein 2 Antibody on Influenza Virus-Induced Pneumonia in Mice

Shinya Sakai,1 Hiroshi Kawamata,1 Naoki Mantani,1 Toshiaki Kogure,1 Yutaka Shimada,1 Katsutoshi Terasawa,1 Takeshi Sakai,2 Nobuko Imanishi,3 and Hiroshi Ochiai3,*

Department of Japanese Oriental Medicine,1 Second Department of Pathology,2 and Department of Human Science,3 Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan

Received 16 August 1999/Accepted 7 December 1999

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 µg 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.

* Corresponding author. Mailing address: Department of Human Science, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Sugitani 2630, Toyama 930-0194, Japan. Phone: 81 076-434-2281, ext. 2415. Fax: 81 076-434-5186. E-mail: ochiai{at}ms.toyama-mpu.ac.jp.

Journal of Virology, March 2000, p. 2472-2476, Vol. 74, No. 5
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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