Contribution of IL-1 to resistance to Streptococcus pneumoniae infection

• Published in: International immunology Vol. 20; no. 9; pp. 1139 - 1146
• Main Authors: Kafka, Daniel, Ling, Eduard, Feldman, Galia, Benharroch, Daniel, Voronov, Elena, Givon-Lavi, Noga, Iwakura, Yoichiro, Dagan, Ron, Apte, Ron N., Mizrachi-Nebenzahl, Yaffa
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.09.2008; Oxford Publishing Limited (England)
• Subjects: Animals; bacterial; cytokines; Female; Humans; inflammation; Interleukin 1 Receptor Antagonist Protein - genetics; Interleukin 1 Receptor Antagonist Protein - metabolism; Interleukin-1alpha - administration & dosage; Interleukin-1alpha - genetics; Interleukin-1alpha - immunology; Interleukin-1alpha - metabolism; Interleukin-1beta - administration & dosage; Interleukin-1beta - genetics; Interleukin-1beta - immunology; Interleukin-1beta - metabolism; Lung - microbiology; Lung - pathology; Mice; Mice, Inbred BALB C; Mice, Knockout; Nasopharynx - microbiology; Pneumonia, Pneumococcal - drug therapy; Pneumonia, Pneumococcal - immunology; Pneumonia, Pneumococcal - microbiology; Pneumonia, Pneumococcal - mortality; Receptors, Interleukin-1 - genetics; Receptors, Interleukin-1 - metabolism; Streptococcus pneumoniae; Streptococcus pneumoniae - isolation & purification; Streptococcus pneumoniae - pathogenicity; vaccination; cytokines; bacterial; inflammation; vaccination
• ISSN: 0953-8178; 1460-2377
• DOI: 10.1093/intimm/dxn071

The role of IL-1 in susceptibility to Streptococcus pneumoniae infection was studied in mice deficient in genes of the IL-1 family [i.e. IL-1α−/−, IL-1β−/−, IL-1α/β−/− and IL-1R antagonist (IL-1Ra)−/− mice] following intra-nasal inoculation. Intra-nasal inoculation of S. pneumoniae of IL-1β−/− and IL-1α/β−/− mice displayed significantly lower survival rates and higher nasopharyngeal and lung bacterial load as compared with control, IL-1α−/− and IL-1Ra−/− mice. Treatment of IL-1β−/− mice with rIL-1β significantly improved their survival. A significant increase in blood neutrophils was found in control, IL-1α−/− and IL-1Ra−/− but not in IL-1β−/−and IL-1α/β−/− mice. Local infiltrates of neutrophils and relatively preserved organ architecture were observed in the lungs of IL-1α−/− and control mice. However, S. pneumoniae-infected IL-1β−/−, IL-1α/β−/− and IL-1Ra−/− mice demonstrated diffuse pneumonia and tissue damage. Altogether, all three isoforms contribute to protection against S. pneumoniae; our results point to differential role of IL-1α and IL-1β in the pathogenesis and control of S. pneumoniae infection and suggest that IL-1β has a major role in resistance to primary pneumococcal infection while the role of IL-1α is less important.