title: 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.
abstract: Surgery-induced immunosuppression could influence tumor/host interactions in surgically treated cancer patients. Previous studies have shown that high-dose IL-2 preoperative therapy may neutralize surgery-induced lymphocytopenia. Moreover, experimental studies have demonstrated that 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 therapy with high-dose IL-2 with respect to those obtained with preoperative neuroimmunotherapy consisting of low-dose IL-2 plus MLT. The study included 30 patients with gastrointestinal tract tumors, who were randomized to undergo surgery alone, or surgery plus a preoperative biotherapy with high-dose IL-2 (18 million IU/day subcutaneously for 3 days) or low-dose IL-2 (6 million IU/day subcutaneously for 5 days) plus MLT (40 mg/day orally). Patients underwent surgery within 36 hours from IL-2 interruption. Both IL-2 plus MLT were able to prevent surgery-induced lymphocytopenia. However, mean number of lymphocytes, T lymphocytes 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 immunotherapy with high-dose IL-2 or neuroimmunotherapy with low-dose IL-2 plus MLT preoperatively are tolerated biotherapies, capable of neutralizing surgery-induced lymphocytopenia in cancer patients. Moreover, the study would suggest that the neuroimmunotherapy may induce a more rapid effect on postoperative immune changes with respect to IL-2 alone.
authors.affiliation: Division of Radiation Oncology, S. Gerardo Hospital, Monza, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Lissoni
authors.forename: F
authors.initials: F
authors.lastname: Brivio
authors.forename: O
authors.initials: O
authors.lastname: Brivio
authors.forename: L
authors.initials: L
authors.lastname: Fumagalli
authors.forename: F
authors.initials: F
authors.lastname: Gramazio
authors.forename: M
authors.initials: M
authors.lastname: Rossi
authors.forename: G
authors.initials: G
authors.lastname: Emanuelli
authors.forename: G
authors.initials: G
authors.lastname: Alderi
authors.forename: F
authors.initials: F
authors.lastname: Lavorato
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D007279:Injections, Subcutaneous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008550:Melatonin / Q000008:administration & dosage / Q000627:therapeutic use*; D008875:Middle Aged; D016176:T-Lymphocyte Subsets / Q000276:immunology
chemical_list: D007376:Interleukin-2; D008550:Melatonin