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.
Licht
A-K
AK
Department of Surgery, Ludwig-Maximilians University Munich, Klinikum Grosshadern, 81377 Munich, Germany.
Schinkel
C
C
Zedler
S
S
Schinkel
S
S
Faist
E
E
D000368:Aged; D000925:Anticoagulants / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D016207:Cytokines / Q000097:blood; D004306:Dose-Response Relationship, Immunologic; D004311:Double-Blind Method; D004492:Edetic Acid / Q000494:pharmacology; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology / Q000627:therapeutic use*; D016753:Interleukin-10 / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000276:immunology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D008297:Male; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D019990:Perioperative Care; D010835:Phytohemagglutinins / Q000494:pharmacology; D010949:Plasma / Q000166:cytology / Q000187:drug effects / Q000276:immunology; D011446:Prospective Studies; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000276:immunology; D011994:Recombinant Proteins; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D013997:Time Factors
D000925:Anticoagulants; D016207:Cytokines; D007376:Interleukin-2; D010835:Phytohemagglutinins; D015375:Receptors, Interleukin-2; D011994:Recombinant Proteins; D016753:Interleukin-10; D015847:Interleukin-4; D007371:Interferon-gamma; D004492:Edetic Acid