Am. J. Respir. Crit. Care Med., Volume 161, Number 1, January 2000, 110-117

Role of Interferon- and Nitric Oxide in Pulmonary Edema and Death Induced by Lipopolysaccharide

HUBERTINE HEREMANS, CHRISTIANE DILLEN, MARLEEN GROENEN, PATRICK MATTHYS, and ALFONS BILLIAU

Laboratory of Immunobiology, Rega Institute, University of Leuven, Faculty of Medicine, Leuven, Belgium

Mice given lipopolysaccharide (LPS) intravenously developed lung edema, which was maximum after 6 h. Tumor necrosis factor, interleukin 12 (IL-12), IL-6, and interferon- (IFN-) appeared in the serum, and levels of nitrogen oxide (NO) derivatives were increased in serum and bronchoalveolar fluid. Mice pretreated with neutralizing anti-IFN- antibodies had lower serum levels of IFN-, and fewer died. However, levels of other cytokines and NO derivatives as well as lung edema were unchanged. If IFN- and LPS were given together, pulmonary edema was less, but levels of cytokines and NO derivatives in serum were raised, and the mortality was greater. IFN- receptor knockout mice had more edema after LPS, but were less sensitive to the lethal effects. Treatment with anti-IL-12 antibody inhibited IFN- induction and reduced mortality, but had no effect on the lung edema; exogenous IL-12 also failed to affect edema, but boosted serum cytokine levels and increased the mortality. Aminoguanidine, an inhibitor of NO synthase, protected against pulmonary edema, but did not modify the lethal effects of LPS. Clearly, in this model, early pulmonary edema and lethality are not directly related, and induced IFN- has no role in causing early lung edema, but augments other events that result in death. Heremans H, Dillen C, Groenen M, Matthys P, Billiau A. Role of interferon- and nitric oxide in pulmonary edema and death induced by lipopolysaccharide.

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