INTERFERON-GAMMA ADMINISTRATION INCREASES MONOCYTE HLA-DR ANTIGEN EXPRESSION BUT NOT ENDOGENOUS INTERFERON-PRODUCTION

Objective: To determine the effect of the adjuvant administration of i nterferon gamma on monocyte HLA-DR antigen expression and mitogen-stim ulated interferon gamma production following injury. Design: Double-bl ind, randomized, placebo-controlled trial. Setting: University Hospita l, Newark, NJ; a level I trauma center. Patients: Persons older than 1 6 years with an Injury Severity Score greater than 20 and documented b acterial contamination at the time of injury (N=98). Interventions: Re combinant human interferon gamma (n=46; 0.1 mg subcutaneously) or plac ebo (n=52) was given for 10 days following injury. Outcomes: Incidence of major infection, monocyte and lymphocyte cell surface antigen expr ession, and interferon gamma production at multiple time points follow ing injury. Results: Peripheral monocyte HLA-DR was measured as percen t of cells staining positive and as mean channel fluorescence. Both va lues were significantly increased in the interferon gamma group compar ed with the placebo group on days 3, 5, 8, and 11. The incidence of ma jor infection was unaffected by interferon gamma administration. Infec tion decreased percent of HLA-DR-positive monocytes and mean channel f luorescence as compared with noninfected patients on postinjury days 8 and 11 in the placebo group but not in the interferon gamma group. In terferon gamma production improved from 3+/-3 U/mL on day 1 to 15+/-10 U/mL by day 30 but was always significantly lower than normal (25+/-3 [mean+/-SD] U/mL). Interferon gamma production was unaffected by eith er infection or interferon gamma administration. Conclusions: Interfer on gamma administration after injury stimulated monocyte HLA-DR antige n expression and density but failed to improve interferon gamma produc tion, a T-cell-mediated function. The incidence of infection was not d ecreased by the administration of interferon gamma for 10 days. Improv ement in monocyte HLA-DR antigen expression did not correlate with a g lobal restoration of immune function, and other interventions will be necessary to decrease infection after injury.