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Am J Physiol Lung Cell Mol Physiol 282: L285-L290, 2002. First published October 26, 2001; doi:10.1152/ajplung.00461.2000
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Vol. 282, Issue 2, L285-L290, February 2002

Role of interleukin-1 in the pulmonary immune response during Pseudomonas aeruginosa pneumonia

Marc J. Schultz1,2, Anita W. Rijneveld1, Sandrine Florquin3, Carl K. Edwards4, Charles A. Dinarello5, and Tom van der Poll1,6

Departments of 1 Experimental Internal Medicine, 2 Intensive Care Medicine, 3 Pathology, and 6 Infectious Diseases, Tropical Medicine, and AIDS, Academic Medical Center of Amsterdam, 1105 AZ Amsterdam, The Netherlands; 4 Amgen, Incorporated, Thousand Oaks, California 91320; and 5 University of Colorado Health Sciences Center, Denver, Colorado 80262

Pneumonia is associated with elevated concentrations of the proinflammatory cytokine interleukin (IL)-1 in the pulmonary compartment. To study the role of IL-1 in the pathogenesis of Pseudomonas pneumonia, IL-1 receptor type 1 gene-deficient (IL-1R -/-) mice and wild-type mice were intranasally inoculated with Pseudomonas aeruginosa. The absence of the IL-1 signal attenuated the outgrowth of Pseudomonas in lungs, as reflected by an increasing number of colony-forming units (cfu) during Pseudomonas pneumonia in wild-type mice and a concurrently decreasing number of cfu during pulmonary infection in IL-1R -/- mice (P < 0.05, IL-1R -/- mice vs. wild-type mice). Influx of neutrophils was decreased in bronchoalveolar lavage fluids in IL-1R -/- mice compared with wild-type mice. Similarly, lung levels of cytokines (tumor necrosis factor-alpha , IL-6) and chemokines (macrophage inflammatory protein-2 and KC) were lower in IL-1R -/- mice 24 h postinoculation. Consistent with results obtained in IL-1R -/- mice, treatment of wild-type mice with IL-1R antagonist also diminished outgrowth of Pseudomonas when compared with wild-type mice treated with vehicle (P < 0.05). These results demonstrate that an absence or reduction in endogenous IL-1 activity improves host defense against Pseudomonas pneumonia while suppressing the inflammatory response.

tumor necrosis factor-alpha ; cytokines


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