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Updated: Sep 19, 2025
Experimental Infection with Listeria monocytogenes as a Model for Studying Host Interferon-γ Responses
Published on: November 16, 2016
Attenuated interferon-γ following injury is associated with chronic critical illness
Joseph Cuschieri1, Lucy Z Kornblith, Hashem Kalthoum
1From the Department of Surgery (J.C., L.Z.K., H.K., S.C.), University of California San Francisco, San Francisco California (S.P.), University of California San Francisco; and Department of Pediatrics (A.P.), University of Washington, Seattle, Washington.
Objective:
Altered genomic expression of interferon (IFN)-γ has been demonstrated to be associated with the development of organ failure following severe injury. Altered expression of IFN-γ on innate immunity and long-term outcomes have not been previously examined. The purpose of this study was to determine the effect that IFN-γ plays on monocyte function and development of chronic critical illness (CCI).
Methods:
Severely injured patients were prospectively evaluated in a development cohort (n = 124). Blood was drawn within 12 hours of injury. Plasma IFN-γ was determined by immune-assay. Clinical and outcome data were prospectively obtained for 1 year. Within this development cohort, a plasma IFN-γ level associated with CCI was determined. This IFN-γ level was analyzed within a separate prospective validation cohort (n = 78). Blood samples in this validation cohort underwent analysis for monocyte activation.
Results:
In the development cohort, an IFN-γ ≤ 50 pg/mL was associated with the development of CCI. This IFN-γ level was independently associated with CCI in the developmental cohort after adjusting for age, Injury Severity Score, lactate concentration, and blood transfusions. An IFN-γ ≤ 50 pg/mL within the validation cohort was associated with a statistically significant increase in CCI, nosocomial infection, poor discharge disposition, and 1-year mortality (25% vs. 4%, p = 0.005). Consistent with the development of CCI, attenuated IFN-γ was associated with decreased monocyte activation and surface human leukocyte antigen-DR expression.
Conclusion:
Decreased IFN-γ is predictive of CCI development. This reduction in IFN-γ is associated with a reduction in human leukocyte antigen-DR and monocyte activation, which may result in the development of CCI, increased nosocomial infections, and poor long-term outcomes. Interferon-γ levels early following injury may be useful as a biomarker for prognosis and to serve to identify patients who could benefit from IFN-γ administration or other novel therapeutic interventions to prevent long-term complications.
Level Of Evidence:
Prognostic and Epidemiological; Level III.
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