Am. J. Respir. Crit. Care Med., Volume 161, Number 3, March 2000, 1030-1036

Importance of Interleukin-8 in the Development of Reexpansion Lung Injury in Rabbits

MORIO NAKAMURA, SEITARO FUJISHIMA, MAKOTO SAWAFUJI, AKITOSHI ISHIZAKA, TSUYOSHI OGUMA, KENZO SOEJIMA, HIROAKI MATSUBARA, SADATOMO TASAKA, KOJI KIKUCHI, KOICHI KOBAYASHI, EIJI IKEDA, MICHAEL SADICK, CAROLINE A. HEBERT, NAOKI AIKAWA, MINORU KANAZAWA, and KAZUHIRO YAMAGUCHI

Departments of Medicine, Emergency and Critical Care Medicine, Surgery, and Pathology, School of Medicine, Keio University, Tokyo, Japan; and Immunology Research, Genentech Inc., South San Francisco, California

Reexpansion of a collapsed lung induces increased microvascular permeability leading to reexpansion pulmonary edema (REPE). This study was designed to prove the hypothesis that local overproduction of interleukin-8 (IL-8) induces inflammatory cell accumulation which leads to the induction of REPE. Initially, we examined the detailed characteristics of a rabbit model of REPE in association with IL-8 production and its mRNA expression. The lung tissue to plasma ratio of radiolabeled albumin (T/P ratio), the lung wet to dry ratio, and bronchoalveolar lavage (BAL) neutrophil counts were significantly increased in the reexpanded lung. IL-8 concentrations and mRNA expression were significantly increased in the reexpanded lung homogenate. Immunohistochemically, alveolar macrophages (AMs) and epithelial cells in the reexpanded lung and AMs in the collapsed lung were positive for IL-8. Second, we examined the effect of pretreatment with a specific monoclonal anti-IL-8 antibody (Ab) or control IgG on the development of REPE. The T/P ratio and BAL neutrophil counts were conspicuously decreased by pretreatment with anti-IL-8 Ab, but not with control IgG. On a histopathological study, lung injury and leukocyte infiltration were attenuated by the pretreatment with anti-IL-8 Ab. In conclusion, IL-8 production is enhanced in the reexpanded lung, and contributes to the development of REPE. The pretreatment with anti-IL-8 antibody may be useful as a novel protective therapy for this disease. Nakamura M, Fujishima S, Sawafuji M, Ishizaka A, Oguma T, Soejima K, Matsubara H, Tasaka S, Kikuchi K, Kobayashi K, Ikeda E, Sadick M, Hebert CA, Aikawa N, Kanazawa M, Yamaguchi K. Importance of interleukin-8 in the development of reexpansion lung injury in rabbits.

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