CXC chemokines are major chemoattractants for pulmonary polymorphonuclear leukocyte (PMNL) recruitment. To study the effects of interferon (IFN)-gamma on the pulmonary chemokine response to lipopolysaccharide (LPS) challenge, rats were treated with intratracheal IFN-gamma (1x10(5) U/rat) 24 h before an intratracheal LPS (100 microg/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-gamma enhanced these responses. IFN-gamma also increased LPS-induced tumor necrosis factor (TNF)-alpha in BAL fluid. LPS-induced TNF-alpha and CINC mRNA expression in alveolar macrophages was increased by IFN-gamma. CD11b/c and CD18 expression on circulating PMNLs was not affected by IFN-gamma, nor was the chemotaxis of these cells. IFN-gamma increases the pulmonary CXC chemokine response, which may serve as one mechanism underlying enhanced PMNL delivery into the lung.