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.
Saperstein
Sara
S
Department of Environmental Medicine, University of Rochester School of Medicine, Rochester, NY 14642, USA.
Huyck
Heidie
H
Kimball
Elizabeth
E
Johnston
Carl
C
Finkelstein
Jacob
J
Pryhuber
Gloria
G
D000208:Acute Disease; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D054426:Chemokine CXCL2 / Q000032:analysis; D020287:In Situ Nick-End Labeling; D053583:Interleukin-1beta / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000502:physiology; D011014:Pneumonia / Q000209:etiology*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000032:analysis; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000032:analysis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D054426:Chemokine CXCL2; C404915:Cxcl2 protein, mouse; D053583:Interleukin-1beta; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D014409:Tumor Necrosis Factor-alpha