Research Article The Effects of Interleukin-1β in Tumor Necrosis Factor-α-Induced Acute Pulmonary Inflammation inMice

We determined the role of interleukin-1β (IL-1β) signaling on tumor necrosis factor alpha-induced (TNF-α) lung neutrophil influx as well as neutrophil chemoattractant macrophage inflammatory protein (MIP-2) and KC and soluble TNF-α receptor (TNFR) levels utilizing wildtype (WT), TNF receptor double knockout (TNFR1/TNFR2 KO), and IL-1β KO mice after oropharyngeal instillation with TNF-α. A significant increase in neutrophil accumulation in bronchoalveolar lavage fluid (BALF) and lung interstitium was detected in the WT mice six hours after TNF-α exposure. This correlated with an increase in BALF MIP-2. In contrast, BALF neutrophil numbers were not increased by TNF-α treatment of IL-1β KOs, correlating with a failure to induce BALF MIP-2 and a trend toward increased BALF soluble TNFR1. TNF-α-instillation increased lavage and serum KC and soluble TNFR2 irrespective of IL-1β expression. These results suggest IL-1β contributes, in part, to TNF-α-mediated, chemokine release, and neutrophil recruitment to the lung, potentially associated with altered soluble TNFR1 release into the BALF. Copyright © 2009 Sara Saperstein et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. 1