The Effects of Interleukin-1βin Tumor Necrosis Factor-α-Induced Acute Pulmonary Inflammation in Mice

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-αreceptor (TNFR) levels utilizing wildtype (WT), TNF receptor double knockout (TNFR1/TNFR2 KO), and IL-1βKO 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-αexposure. This correlated with an increase in BALF MIP-2. In contrast, BALF neutrophil numbers were not increased by TNF-αtreatment of IL-1βKOs, 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-1βexpression. These results suggest IL-1βcontributes, in part, to TNF-α-mediated, chemokine release, and neutrophil recruitment to the lung, potentially associated with altered soluble TNFR1 release into the BALF.