The effects of interleukin-1ß in tumor necrosis factor-β-induced acute pulmonary inflammation in mice

Abstract

We determined the role of interleukin-1 (IL-1 ) signaling on tumor necrosis factor alpha-induced (TNF-) lung neutrophil influx as well as neutrophil chemoattractant macrophage inflammatory protein (MIP-2) and KC and soluble TNF- receptor (TNFR) levels utilizing wildtype (WT), TNF receptor double knockout (TNFR1/TNFR2 KO), and IL-1 KO mice after oropharyngeal instillation with TNF-. A significant increase in neutrophil accumulation in bronchoalveolar lavage fluid (BALF) and lung interstitium was detected in the WT mice six hours after TNF- exposure. This correlated with an increase in BALF MIP-2. In contrast, BALF neutrophil numbers were not increased by TNF- treatment of IL-1 KOs, correlating with a failure to induce BALF MIP-2 and a trend toward increased BALF soluble TNFR1. TNF - instillation increased lavage and serum KC and soluble TNFR2 irrespective of IL-1 expression. These results suggest IL-1 contributes, in part, to TNF - mediated, chemokine release, and neutrophil recruitment to the lung, potentially associated with altered soluble TNFR1 release into the BALF.