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Infection and Immunity, December 2004, p. 6892-6901, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.6892-6901.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Gamma Interferon Does Not Enhance Clearance of Pseudomonas aeruginosa but Does Amplify a Proinflammatory Response in a Murine Model of Postseptic Immunosuppression

E. D. Murphey,1,2* David N. Herndon,1,3 and Edward R. Sherwood1,2

Department of Anesthesiology,1 Department of Surgery, University of Texas Medical Branch,3 Shriners Hospital for Children-Galveston Burns Unit, Galveston, Texas2

Received 1 July 2004/ Returned for modification 30 July 2004/ Accepted 24 August 2004

Patients that have suffered a major injury may sustain a period of immunocompromise and altered Th1/Th2 cytokine balance that can predispose them to opportunistic infections. Pseudomonas aeruginosa is frequently a causative organism for nosocomial infections in critically ill patients and is associated with high mortality. We previously mimicked this clinical scenario by challenging mice with P. aeruginosa 5 days after a cecal ligation and puncture (CLP) procedure. Mice that were subjected to CLP had reduced ability to clear bacteria, significantly lower gamma interferon (IFN-{gamma}) concentrations in plasma, and significantly elevated levels of interleukin 10 (IL-10) in plasma in response to the Pseudomonas challenge compared to uninjured control mice. We investigated the significance of the alteration in IFN-{gamma} by administering recombinant IFN-{gamma} to post-CLP mice at the time of Pseudomonas challenge and by challenging IFN-{gamma} knockout (IFN-{gamma} KO) mice with Pseudomonas. Administration of IFN-{gamma} to post-CLP mice attenuated IL-10 secretion and enhanced IL-12 secretion but did not improve bacterial clearance or survival after Pseudomonas challenge. Furthermore, IFN-{gamma} KO mice had significantly higher plasma IL-10 concentrations but did not exhibit impaired bacterial clearance or increased mortality following Pseudomonas challenge. These data indicate that systemic administration of IFN-{gamma} effectively reverses alterations in immune function that are commonly associated with immunosuppression in critically injured mice but does not improve bacterial clearance or survival following Pseudomonas challenge. Further, endogenous IFN-{gamma} does not appear to contribute significantly to early clearance of Pseudomonas bacteremia, nor does it affect the mortality rate after a lethal Pseudomonas challenge.

* Department of Anesthesiology, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0591. Phone: (409) 772-1221. Fax: (409) 770-6919. E-mail: edmurphe{at}utmb.edu.

Editor: F. C. Fang

Infection and Immunity, December 2004, p. 6892-6901, Vol. 72, No. 12
0019-9567/04/$08.00+0     DOI: 10.1128/IAI.72.12.6892-6901.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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