Interferon‐γ Enhances the Pulmonary CXC Chemokine Response to Intratracheal Lipopolysaccharide Challenge

Abstract

CXC chemokines are major chemoattractants for pulmonary polymorphonuclear leukocyte (PMNL) recruitment. To study the effects of interferon (IFN)–γ on the pulmonary chemokine response to lipopolysaccharide (LPS) challenge, rats were treated with intratracheal IFN-γ (1×10⁵ U/rat) 24 h before an intratracheal LPS (100 μg/rat) challenge. Intratracheal LPS caused significant increases in both cytokine-induced neutrophil chemoattractant (CINC) and macrophage inflammatory protein–2 in bronchoalveolar lavage (BAL) fluid and pulmonary PMNL recruitment. IFN-γ enhanced these responses. IFN-γ also increased LPS-induced tumor necrosis factor (TNF)–α in BAL fluid. LPS-induced TNF-α and CINC mRNA expression in alveolar macrophages was increased by IFN-γ. CD11b/c and CD18 expression on circulating PMNLs was not affected by IFN-γ, nor was the chemotaxis of these cells. IFN-γ increases the pulmonary CXC chemokine response, which may serve as one mechanism underlying enhanced PMNL delivery into the lung