Role of the type 1 TNF receptor in lung inflammation after inhalation of endotoxin or Pseudomonas aeruginosa

To determine the roles of the type 1 tumor necrosis factor (TNF) receptor ( TNFR1) in lung inflammation and antibacterial defense, we exposed transgeni c mice lacking TNFR1 [TNFR1(-/-)] and wild-type control mice to aerosolized lipopolysaccharide or Pseudomonas aeruginosa. After LPS, bronchoalveolar l avage fluid (BALF) from TNFR1(-/-) mice contained fewer neutrophils and les s macrophage inflammatory protein-2 than BALF from control mice. TNF-alpha, interleukin-1 beta, and total protein levels in BALF as well as tissue int ercellular adhesion molecule-1 expression did not differ between the two gr oups. In contrast, lung inflammation and bacterial clearance after infectio n were augmented in TNFR1(-/-) mice. BALF from infected TNFR1(-/-) mice con tained more neutrophils and TNF-alpha and less interleukin-1 beta and macro phage inflammatory protein-a than that from control mice, but protein level s were similarly elevated in both groups. Lung inflammation and bacterial c learance were also augmented in mice lacking both TNF receptors. Thus TNFR1 facilitates neutrophil recruitment after inhalation of lipopolysaccharide, in part by augmenting chemokine induction. In contrast, TNFR1 attenuates l ung inflammation in response to live bacteria but does not contribute to in creased lung permeability and is not required for the elimination of P. aer uginosa.