title: Interleukin-2, melatonin and interleukin-12 as a possible neuroimmune combination in the biotherapy of cancer.
abstract: Suppressive events induced by macrophages and TH2 lymphocytes would represent the most important factors responsible for the in vivo reduced efficacy of IL-2 cancer immunotherapy. Previous studies have shown that IL-3 or the pineal hormone MLT may abrogate macrophage-related suppressive events during IL-2 immunotherapy, while TH2-mediated immunosuppression is not neutralized by MLT or IL-3. On the basis of previous experimental data suggesting the inhibitory effect of IL-12 on TH2 activation, this preliminary study has been performed in an attempt to evaluate the influence of IL-12 on TH2 stimulation induced by IL-2 alone or IL-2 plus MLT, by evaluating the release of IL-10, which represents the main suppressive factor produced by TH2 lymphocytes. Pure lymphocyte cultures were incubated for 4 days with IL-2 (100 Cetus U/ml), MLT (100 pg/ml), IL-12 (1 ng/ml), IL-2 plus MLT, IL-2 plus IL-12 or IL-2 plus MLT and IL-12. Mean medium concentrations of IL-10 were measured by Elisa. IL-2 alone significantly stimulated IL-10 secretion with respect to the control medium alone, while no difference was observed with MLT alone or IL-12. IL-2-induced stimulation of IL-10 secretion was not abrogated by a concomitant MLT incubation. On the contrary, IL-12 significantly diminished IL-10 release in response to IL-2, and this inhibitory effect was more pronounced when IL-2 was added in association with both IL-12 and MLT. This preliminary study would suggest that the two most important immunosuppressive events occurring during IL-2 therapy, which are mediated by macrophages and TH2-lymphocytes, may be abrogated by a concomitant administration of MLT and IL-12, respectively. Therefore, the association of IL-12 could further amplify IL-2 efficacy with respect to IL-2 alone or IL-2 plus MLT.
authors.affiliation: Division of Radiotherapy, San Gerardo Hospital, Monza (Milano), Italy.
authors.forename: P
authors.initials: P
authors.lastname: Lissoni
authors.forename: S
authors.initials: S
authors.lastname: Pittalis
authors.forename: F
authors.initials: F
authors.lastname: Rovelli
authors.forename: L
authors.initials: L
authors.lastname: Vigorè
authors.forename: M G
authors.initials: MG
authors.lastname: Roselli
authors.forename: F
authors.initials: F
authors.lastname: Brivio
mesh_terms: D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D066298:In Vitro Techniques; D016753:Interleukin-10 / Q000378:metabolism; D018664:Interleukin-12 / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D008213:Lymphocyte Activation / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008550:Melatonin / Q000008:administration & dosage*; D009369:Neoplasms / Q000276:immunology / Q000628:therapy*; D015213:Neuroimmunomodulation; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D007376:Interleukin-2; D016753:Interleukin-10; D018664:Interleukin-12; D008550:Melatonin