Role of interleukin-1 in the pulmonary immune response during Pseudomonas aeruginosa pneumonia.
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.
Schultz
Marc J
MJ
Department of Experimental Internal Medicine, Tropical Medicine, and AIDS, Academic Medical Center of Amsterdam, 1105 AZ Amsterdam, The Netherlands. m.j.schultz@amc.uva.nl
Rijneveld
Anita W
AW
Florquin
Sandrine
S
Edwards
Carl K
CK
Dinarello
Charles A
CA
van der Poll
Tom
T
D000818:Animals; D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines / Q000378:metabolism; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000378:metabolism; D005260:Female; D006133:Growth Substances / Q000378:metabolism; D036341:Intercellular Signaling Peptides and Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000276:immunology* / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018410:Pneumonia, Bacterial / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D011550:Pseudomonas aeruginosa; D017472:Receptors, Interleukin-1 / Q000235:genetics*; D012795:Sialoglycoproteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D054360:Chemokine CXCL1; D054426:Chemokine CXCL2; D018925:Chemokines; D019743:Chemokines, CXC; D002630:Chemotactic Factors; C475895:Cxcl1 protein, mouse; C404915:Cxcl2 protein, mouse; D006133:Growth Substances; C507764:Il1rn protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D017472:Receptors, Interleukin-1; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha