Abstract

Many aspects of the normal immune response are depressed after severe injury. Reduced monocyte human leukocyte antigen-DR (HLA-DR) levels have closely correlated with the development of major infection. After a pilot study with recombinant interferon-gamma (rIFN-gamma) showed restoration of depressed HLA-DR levels after major injury, a multicenter, prospective, randomized, double-blind trial was conducted. Two hundred thirteen trauma patients who were at high risk of infection received either placebo or rIFN-gamma (100 micrograms) subcutaneously each day for 10 days after admission. One hundred ninety-three patients were evaluable with respect to primary end points. Patients treated with rIFN-gamma were older (p = 0.10) and had more severe modes of injury (p = 0.02). By the third day, both monocyte HLA-DR antigen expression and outcome predictive score were significantly better in the rIFN-gamma-treated group than in the placebo group (p = 0.0001 and p = 0.0006, respectively). Nine deaths occurred in patients treated with rIFN-gamma compared with 12 deaths in the placebo group (p = 0.46). Major infections requiring surgical drainage or debridement occurred in 17 patients treated with rIFN-gamma compared with 22 treated with placebo. No difference between treatment arms was noted in overall major or minor infection rates, but there were fewer severe infections that required reoperation or computer tomographic-guided drainage in patients receiving IFN-gamma. While these results suggest that rIFN-gamma may be useful in some aspects of infection in the patient with severe trauma, a larger trial with longer treatment will be needed to prove the comprehensive value of rIFN-gamma.