Low dose oral administration of cytokines for treatment of allergic asthma

• Published in: Pulmonary pharmacology & therapeutics Vol. 22; no. 6; pp. 497 - 510
• Main Authors: Gariboldi, Silvia, Palazzo, Marco, Zanobbio, Laura, Dusio, Giuseppina F, Mauro, Valentina, Solimene, Umberto, Cardani, Diego, Mantovani, Martina, Rumio, Cristiano
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-12-2009
• Subjects: Allergy; Animals; Asthma - drug therapy; Asthma - pathology; Bronchial Hyperreactivity - drug therapy; Bronchial Hyperreactivity - physiopathology; Bronchoalveolar Lavage Fluid - cytology; CD11c Antigen - immunology; Cytokines; Cytokines - administration & dosage; Cytokines - therapeutic use; Dendritic Cells - drug effects; Dose-Response Relationship, Drug; Enzyme-Linked Immunosorbent Assay; IFN-γ; IL-12; Interferon-gamma - administration & dosage; Interferon-gamma - therapeutic use; Interleukin-12 - administration & dosage; Interleukin-12 - therapeutic use; Lung; Lung - immunology; Lung - pathology; Male; Medical Education; Mice; Mouse; Pulmonary/Respiratory; Recombinant Proteins - therapeutic use; Respiratory Hypersensitivity - drug therapy; Respiratory Hypersensitivity - pathology; Solutions; Spleen - cytology; Spleen - drug effects; Th1 Cells - drug effects; Th1 Cells - immunology; Th1/Th2 Cells; Th2 Cells - drug effects; Th2 Cells - immunology; Allergy; Th1/Th2 Cells; IFN-γ; Cytokines; Mouse; Lung; IL-12
• ISSN: 1094-5539; 1522-9629
• DOI: 10.1016/j.pupt.2009.05.002

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-γ 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-γ 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.