PREOPERATIVE NEUROIMMUNOTHERAPY WITH SUBCUTANEONS LOW-DOSE INTERLEUKIN-2 AND MELATONIN IN PATIENTS WITH GASTROINTESTINAL TUMORS - ITS EFFICACY IN PREVENTING SURGERY-INDUCED LYMPHOCYTOPENIA

Our previous studies have shown that a preoperative injection of high dose IL-2 is able to abrogate surgery-induced immunosuppression in col orectal cancer patients. Moreover, our previous clinical investigation s have indicated the possibility of amplifying IL-2 activity by a conc omitant administration of the pineal immunomodulating hormone melatoni n (MLT). On this basis, a biological study was performed to investigat e the immune effects of a preoperative biotherapy consisting of low-do se IL-2 plus MLT in patients with gastrointestinal tumors. The study i ncluded 20 consecutive patients with gastrointestinal tract tumors, wh o underwent radical or palliative surgery. Patients were randomized to receive no preoperative treatment or a presurgical neuroimmunotherape utic regimen consisting of low dose of IL-2 and MLT. IL-2 was injected subcutaneously at 3 million IU twice/day for 5 days in combination wi th MLT at 40 mg/day in the evening. Patients underwent surgery within 36 h from the last IL-2 injection. The mean number of lymphocytes, T l ymphocytes and NK cells significantly decreased during the postoperati ve period in control patients, whereas it increased in patients pre-tr eated by immunotherapy. CD25-positive mean cell number increased in bo th groups of patients; however, postoperative mean number of CD25 expr essing cells was significantly higher in patients pretreated with IL-2 and MLT than in controls. No immunotherapy-related toxicity occurred. This preliminary study would suggest that a neuroimmunotherapeutic re gimen with low-dose IL-2 and MLT given preoperatively is a well tolera ted therapy, which is able to prevent surgery-induced lymphocytopenia in cancer patients. This perioperative manipulation of host anticancer defenses could have a prognostic role in the clinical course of the n eoplastic disease.