The effects of interleukin-1beta in tumor necrosis factor-alpha-induced acute pulmonary inflammation in mice.

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