Effects of perioperative recombinant human IFN-gamma (rHuIFN-gamma) application in vivo on T cell response

In spite of the well-known immunoregulatory effects of recombinant human interferon-gamma (rHuIFN-gamma), in vitro clinical trials in trauma patients remain inconclusive. In vitro studies have shown that IFN-gamma has an effect on lymphocyte responses in addition to immunomodulatory effects on the monocyte/macrophage system. To investigate the in vivo effect of rHuIFN-gamma perioperatively on lymphocyte behavior in surgical patients, we studied 46 anergic patients undergoing major surgery. Treated patients (T, n = 24) received 100 microg rHuIFN-gamma subcutaneously (s.c.), and control patients (C, n = 22) received a placebo on preoperative days -7, -5, and -3 in a controlled, double-blinded placebo trial. Whole blood cultures were stimulated with mitogen on perioperative days, and cytokines were investigated in the supernatants. Interleukin-2 receptor (IL-2R) levels were significantly elevated in the treatment arm during the postoperative period (p < 0.05). The postoperative enhancement of IL-4 in C was completely attenuated in T (p < 0.05). IL-2 levels were elevated perioperatively in T but not in C. No significant effect of rHuIFN-gamma could be demonstrated on IL-10 or lymphocyte proliferation in vitro. From this pilot study, we conclude that preoperative in vivo immunomodulation of lymphocyte function with rHuIFN-gamma in anergic patients is effective. It improves immunoreactivity, as shown by elevated IL-2R levels. Elevated IL-2 and suppressed IL-4 levels indicate a shift toward a Th1-driven lymphocyte response.