title: Low dose oral administration of cytokines for treatment of allergic asthma.
abstract: Many inflammatory diseases are characterized by an imbalance among lymphocyte populations, in particular Th1, Th2 and the recently described Th17 cells. The Th1/Th2 imbalance is linked to many factors, but certainly the role of cytokines is essential. In Th2 diseases IL-4 expression is predominant, while Th1 pathologies are characterized by high expression of IFN-gamma and IL-12. Though today the therapeutical proposal for many inflammatory diseases aims to re-establish normal levels of Th1/Th2 cytokines, the pharmacological use of cytokines, which are very active molecules, is limited by the possible collateral effects. Therefore, our study aims to determine, in a murine model of allergic asthma, the possible therapeutic activity of low dose cytokines solutions, mechanically activated. We found that oral administration of low doses IL-12 plus IFN-gamma is able to solve the bronchial hyperresponsiveness condition of mice, establishing normal cytokine levels. The anti-asthma activity was confirmed by histological analysis of lungs and broncho-alveolar lavage fluid cell count. Serum ovalbumin-specific IgE was also significantly inhibited by treatment with low dose activated cytokines solution. These findings may suggest a novel approach to diseases which involve a Th1/Th2 imbalance.
authors.affiliation: iMIL - italian Mucosal Immunity Laboratory, Department of Human Morphology and Biomedical Sciences Città Studi, Università degli Studi di Milano, via Mangiagalli 31, 20133 Milano, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Gariboldi
authors.forename: Marco
authors.initials: M
authors.lastname: Palazzo
authors.forename: Laura
authors.initials: L
authors.lastname: Zanobbio
authors.forename: Giuseppina F
authors.initials: GF
authors.lastname: Dusio
authors.forename: Valentina
authors.initials: V
authors.lastname: Mauro
authors.forename: Umberto
authors.initials: U
authors.lastname: Solimene
authors.forename: Diego
authors.initials: D
authors.lastname: Cardani
authors.forename: Martina
authors.initials: M
authors.lastname: Mantovani
authors.forename: Cristiano
authors.initials: C
authors.lastname: Rumio
mesh_terms: D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D039521:CD11c Antigen / Q000276:immunology; D016207:Cytokines / Q000008:administration & dosage / Q000627:therapeutic use*; D003713:Dendritic Cells / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D007371:Interferon-gamma / Q000008:administration & dosage / Q000627:therapeutic use*; D018664:Interleukin-12 / Q000008:administration & dosage / Q000627:therapeutic use*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D011994:Recombinant Proteins / Q000627:therapeutic use; D012130:Respiratory Hypersensitivity / Q000188:drug therapy* / Q000473:pathology; D012996:Solutions; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D018417:Th1 Cells / Q000187:drug effects / Q000276:immunology; D018418:Th2 Cells / Q000187:drug effects / Q000276:immunology
chemical_list: D039521:CD11c Antigen; D016207:Cytokines; D011994:Recombinant Proteins; D012996:Solutions; D018664:Interleukin-12; D007371:Interferon-gamma