Attenuated interferon-γ following injury is associated with chronic critical illness.

Abstract

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). 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. 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. 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. Prognostic and Epidemiological; Level III.