The Effects of Interleukin-1β in 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-α receptor (TNFR) levels utilizing wildtype (WT), TNF receptor double...

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Bibliographic Details
Main Authors: Sara Saperstein, Heidie Huyck, Elizabeth Kimball, Carl Johnston, Jacob Finkelstein, Gloria Pryhuber
Format: Article
Language:English
Published: Wiley 2009-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2009/958658
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Summary: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.
ISSN:0962-9351
1466-1861