IMMUNE EFFECTS OF PREOPERATIVE IMMUNOTHERAPY WITH HIGH-DOSE SUBCUTANEOUS INTERLEUKIN-2 VERSUS NEUROIMMUNOTHERAPY WITH LOW-DOSE INTERLEUKIN-2 PLUS THE NEUROHORMONE MELATONIN IN GASTROINTESTINAL-TRACT TUMOR PATIENTS

Surgery-induced immunosuppression could influence tumor/host interacti ons in surgically treated cancer patients. Previous studies have shown that high-dose IL-2 preoperative therapy may neutralize surgery-induc ed lymphocytopenia. Moreover, experimental studies have demonstrated t hat the immunomodulating neurohormone melatonin (MLT) may amplify IL-2 activity and reduce its dose required to activate the immune system. On this basis, we have compared the immune effects of presurgical ther apy with high-dose IL-2 with respect to those obtained with preoperati ve neuroimmunotherapy consisting of low-dose IL-2 plus MLT. The study included 30 patients with gastrointestinal tract tumors, who were rand omized to undergo surgery alone, or surgery plus a preoperative biothe rapy with high-close IL-2 (18 million IU/day subcutaneously for 3 days ) or low-dose IL-2 (6 million IU/day subcutaneously for 5 days) plus M LT (40 mg/day orally). Patients underwent surgery within 36 hours from IL-2 interruption. Both IL-2 plus MLT were able to prevent surgery-in duced lymphocytopenia. However, mean number of lymphocytes, T lymphocy tes and T helper lymphocytes observed on day 1 of postoperative period was significantly higher in patients treated with IL-2 plus MLT than in those receiving IL-2 alone. Moreover, toxicity was less in patients treated with IL-2 and MLT. This biological study shows that both immu notherapy with high-dose IL-2 or neuroimmunotherapy with low-dose IL-2 plus MLT preoperatively ave tolerated biotherapies, capable of neutra lizing surgery-induced lymphocytopenia in cancer patients. Moreover, t he study would suggest that the neuroimmunotherapy may induce a more r apid effect on postoperative immune changes with respect to IL-2 alone .