Treatment of bronchial asthma by blockade of GATA-3 expression with nebulized interferon gamma

Objective To investigate the efficacy and the mechanism of the action of nebulized interferon gamma(IFN-γ)in prevention and treatment of bronchial asthma.Methodes Ovalbumin(OVA)adsorbed to alu- minum hydroxide was used to construct clinical bronchial asthma model in BALB/c mice(group C),nebulized IFN-γ12μg was inhaled on day 23 to day 30 once daily.The bronchalveolar lavage fluid(BALF)was collected on day 31,of which the cellular constituents,levels of IL-4,IL-5 and IgE were determined,together with the patho- logic changes and expression of GATA-3 were observed.The normal control group(group A)and the asthmatic model group(group B)consisted of 12 mice for each.Results Decrease of eosinophils(0.005±0.003)was seen in BALF of group C as comparing with group B(0.211±0.067,P＜0.01),the levels of IL-4 [(6.8±3.7) pg/mL]and IL-5 [(12.6±4.8)pg/mL]decreased significantly in comparing with group B [IL-4 (90.5±22.4)pg/mL and IL-5(55.6±10.7)pg/mL,P＜0.01].The serum levels of total IgE [(38.8±9.7)μg/mL]and ovalbumin-spe- cific IgE[(19.2±4.8)U/mL]decreased significantly in comparing with those of group B [(67.2±9.7)μg/mL] and [(34.6±7.8)U/mL,P＜0.01].In group B,there were bronchial smooth muscle hypertrophy,mucosal con- gestion and edema thickening with inflammatory cells infiltration mainly of eosinophils,and abundant mucus throm- bi inside the bronchial lumen.In group C,the above mentioned changes were much more ameliorated.Immunohis- tochemistry showed significant increase of GATA-3 expression in the lung tissue of group B but much lesser than that in group C.Conclusion IFN-γcan inhibit IL-4,IL-5 and the airway inflammation with eosinophilic infiltration and the serum levels of total IgE and ovalbumin-specific IgE,probably through the mechamism of restraining the Th2 reaction by blockade of GATA-3 expression in the lung tissue.(Shanghai Med J,2006,29:640-643)