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International Immunology Advance Access published online on July 1, 2008
International Immunology, doi:10.1093/intimm/dxn071
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Contribution of IL-1 to resistance to Streptococcus pneumoniae infection

Daniel Kafka1,2,5, Eduard Ling3,5, Galia Feldman1,2,5, Daniel Benharroch4,5, Elena Voronov2,5, Noga Givon-Lavi1,5, Yoichiro Iwakura6, Ron Dagan1,5, Ron N. Apte2,5,* and Yaffa Mizrachi-Nebenzahl1,2,5,*

1 Pediatric Infectious Disease Unit, Soroka University Medical Center
2 The Shraga Segal Department of Microbiology and Immunology and the Cancer Center
3 Pediatrics Department ‘B’, Soroka University Medical Center
4 Institute of Pathology, Soroka University Medical Center
5 The Faculty of Health Sciences, Ben Gurion University of the Negev, PO Box 151, Beer Sheva 84101, Israel
6 Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo, Japan

Correspondence to: Correspondence to: Y. M. Nebenzahl; E-mail: ymizr{at}bgu.ac.il

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-1{alpha}–/–, IL-1β–/–, IL-1{alpha}/β–/– and IL-1R antagonist (IL-1Ra)–/– mice] following intra-nasal inoculation. Intra-nasal inoculation of S. pneumoniae of IL-1β–/– and IL-1{alpha}/β–/– mice displayed significantly lower survival rates and higher nasopharyngeal and lung bacterial load as compared with control, IL-1{alpha}–/– 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-1{alpha}–/– and IL-1Ra–/– but not in IL-1β–/–and IL-1{alpha}/β–/– mice. Local infiltrates of neutrophils and relatively preserved organ architecture were observed in the lungs of IL-1{alpha}–/– and control mice. However, S. pneumoniae-infected IL-1β–/–, IL-1{alpha}/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-1{alpha} 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-1{alpha} is less important.

Keywords: bacterial, cytokines, inflammation, vaccination

* Equal contributors to the study

Transmitting editor: I. Pecht

Received 21 February 2008, accepted 4 June 2008.


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