Gamma Interferon Does Not Enhance Clearance ofPseudomonas aeruginosabut Does Amplify a Proinflammatory Response in a Murine Model of Postseptic Immunosuppression

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Abstract
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 aeruginosais 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 withP. aeruginosa5 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 thePseudomonaschallenge 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 ofPseudomonaschallenge and by challenging IFN-γ knockout (IFN-γ KO) mice withPseudomonas. 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 afterPseudomonaschallenge. Furthermore, IFN-γ KO mice had significantly higher plasma IL-10 concentrations but did not exhibit impaired bacterial clearance or increased mortality followingPseudomonaschallenge. 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 followingPseudomonaschallenge. Further, endogenous IFN-γ does not appear to contribute significantly to early clearance ofPseudomonasbacteremia, nor does it affect the mortality rate after a lethalPseudomonaschallenge.