Gamma interferon does not enhance clearance of Pseudomonas aeruginosa but does amplify a proinflammatory response in a murine model of postseptic immunosuppression

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-γ) 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-γ by administering recombinant IFN-γ to post-CLP mice at the time of Pseudomonas challenge and by challenging IFN-γ knockout (IFN-γ KO) mice with Pseudomonas. Administration of IFN-γ 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-γ 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-γ 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-γ does not appear to contribute significantly to early clearance of Pseudomonas bacteremia, nor does it affect the mortality rate after a lethal Pseudomonas challenge.