Regulation of acute lung inflammatory injury by endogenous IL-13.

Using IgG immune complex deposition to trigger acute lung inflammation in rats, we have previously shown that exogenously administered IL-13 suppresses the acute inflammatory response. In the same model, expression of both mRNA and protein for IL-13 has now been detected. Treatment of rats with Ab to IL-13 accentuated the inflammatory response, with significant increases in lung vascular permeability and in the number of neutrophils in bronchoalveolar lavage fluids. In the presence of anti-IL-13, activation of the transcription factor, NF-kappaB, was significantly increased in lung. In addition, anti-IL-13 caused significant increases in bronchoalveolar lavage levels of TNF-alpha, macrophage inflammatory protein-2, and cytokine-inducible neutrophil chemoattractant but no changes in lung vascular ICAM-1. These data suggest that during lung inflammation endogenous IL-13 regulates NF-kappaB activation and related cytokine/chemokine generation, all of which determines the intensity of the lung inflammatory response.