Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents

This Article Full Text Full Text (PDF) PPT slides of all figures Supplemental Material Index Alert me when this article is cited Citation Map Services Email this article Similar articles in this journal Similar articles in PubMed Alert me to new content in the JEM Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wirtz, S. Articles by Neurath, M. F. Search for Related Content PubMed PubMed Citation Articles by Wirtz, S. Articles by Neurath, M. F. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Medline Plus Health Information Sepsis Related Collections Related Article Social Bookmarking                      What's this?

¹ Laboratory of Immunology, I. Medical Clinic, and ² Department of Immunology, University of Mainz, 55131 Mainz, Germany
³ Department of Pathology and Department of Anatomy, Eastern Virginia Medical School, Norfolk, VA 23501
⁴ Gastroenterology Division, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115

CORRESPONDENCE Markus F. Neurath: neurath{at}1-med.klinik.uni-mainz.de

The immune response to bacterial infections must be tightly controlled to guarantee pathogen elimination while preventing tissue damage by uncontrolled inflammation. Here, we demonstrate a key role of interleukin (IL)-27 in regulating this critical balance. IL-27 was rapidly induced during murine experimental peritonitis induced by cecal ligation and puncture (CLP). Furthermore, mice deficient for the EBI3 subunit of IL-27 were resistant to CLP-induced septic peritonitis as compared with wild-type controls, and this effect could be suppressed by injection of recombinant single-chain IL-27. EBI3^–/– mice displayed significantly enhanced neutrophil migration and oxidative burst capacity during CLP, resulting in enhanced bacterial clearance and local control of infection. Subsequent studies demonstrated that IL-27 directly suppresses endotoxin-induced production of reactive oxygen intermediates by isolated primary granulocytes and macrophages. Finally, in vivo blockade of IL-27 function using a newly designed soluble IL-27 receptor fusion protein led to significantly increased survival after CLP as compared with control-treated mice. Collectively, these data identify IL-27 as a key negative regulator of innate immune cell function in septic peritonitis. Furthermore, in vivo blockade of IL-27 is a novel potential therapeutic target for treatment of sepsis.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

• Villarino, A. V., Artis, D., Bezbradica, J. S., Miller, O., Saris, C. J. M., Joyce, S., Hunter, C. A. (2008). IL-27R deficiency delays the onset of colitis and protects from helminth-induced pathology in a model of chronic IBD. Int Immunol 20: 739-752 [Abstract] [Full Text]  
• Huber, M., Steinwald, V., Guralnik, A., Brustle, A., Kleemann, P., Rosenplanter, C., Decker, T., Lohoff, M. (2008). IL-27 inhibits the development of regulatory T cells via STAT3. Int Immunol 20: 223-234 [Abstract] [Full Text]  
• Siebler, J., Wirtz, S., Frenzel, C., Schuchmann, M., Lohse, A. W., Galle, P. R., Neurath, M. F. (2008). Cutting Edge: A Key Pathogenic Role of IL-27 in T Cell- Mediated Hepatitis. J. Immunol. 180: 30-33 [Abstract] [Full Text]  
• Wang, S., Miyazaki, Y., Shinozaki, Y., Yoshida, H. (2007). Augmentation of Antigen-Presenting and Th1-Promoting Functions of Dendritic Cells by WSX-1(IL-27R) Deficiency. J. Immunol. 179: 6421-6428 [Abstract] [Full Text]  
• Neurath, M. F (2007). New therapies for sepsis: focus on the interleukin (IL)12 family member IL27. Ann Rheum Dis 66: iii29-iii31 [Abstract] [Full Text]  
• Molle, C., Nguyen, M., Flamand, V., Renneson, J., Trottein, F., De Wit, D., Willems, F., Goldman, M., Goriely, S. (2007). IL-27 Synthesis Induced by TLR Ligation Critically Depends on IFN Regulatory Factor 3. J. Immunol. 178: 7607-7615 [Abstract] [Full Text]  

Home | Help | Feedback | Subscriptions | Archive | Search

TABLE OF CONTENTS