Low dose oral administration of cytokines for treatment of allergic asthma.
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.
Gariboldi
Silvia
S
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.
Palazzo
Marco
M
Zanobbio
Laura
L
Dusio
Giuseppina F
GF
Mauro
Valentina
V
Solimene
Umberto
U
Cardani
Diego
D
Mantovani
Martina
M
Rumio
Cristiano
C
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
D039521:CD11c Antigen; D016207:Cytokines; D011994:Recombinant Proteins; D012996:Solutions; D018664:Interleukin-12; D007371:Interferon-gamma