Effect Of MIL-12 Plasmid On CD4～+CD25～+ T Cells And Correlative Cytokines In The Asthmatic Model Of Mouse

BACKGROUND:Asthma is a most familiar global chronic disease. Recently the incidence of asthma is increasing. Because of airway inflammation, patients with asthma are more sensitive to the allergens, and the airway will become narrow, the breath will be restricted reversibly, then some symptoms such as cough and gasp will occur. Asthma affects the patients' work and life seriously and brings huge burden to families and society, therefore study on the mechanism in prevention and therapy of asthma will be an important subject in the world. IL-12 is a kind of cytokine secreted by antigen presenting cells such as dendritic cells and macrophages etc. It has been approved that IL-12 controls the airway inflammation of asthma by regulation of Th1/Th2 balance. However, administration of IL-12 recombinant protein directly will bring serious side-effect, so IL-12 gene is transduced into body by a vector such as plasmid and then produces endogenetic IL-12, which has important theoretical and actual significance for prevention and treatment of asthma. Mouse IL-12 (mIL-12) genetic expression plasmid is very effective for asthma, we have obtained some results in the airway inflammation, CD molecules and cytokines.On the base of these, we decide to study the effect of mIL-12plasmid on the percentage of the CD4+CD25+ T cells and the levels of associatedcytokines in asthmatic mice and to explore the possible mechanism.OBJECTIVE:To investigate the efiFect of mouse IL-12 plasmid (mIL-12 plasmid) intramuscularlyadministrated on the percentage of the CD4+CD25+ T cells and the levels ofassociated cytokines in asthmatic mice and to explore the possible mechanism.METHODS:A mouse model of asthma was established by sensitization with ovalbumin (OVA).Forty BALB/c mice were divided into eight groups including asthmatic modelgroup, normal control group, model control group, positive control group treatedwith DXM, empty plasmid prevention control group, empty plasmid treatmentcontrol group, mIL-12 plasmid prevention group, mIL-12 plasmid treatment group.The percentage of CD4+CD25+ T cells in the peripheral blood\marrow andspleen were detected by flow cytometry and the levels of IL-10,TGF- P ,IL-4 andIL-5 in the serum and bronchoalveolar lavage fluids (BALF) were detected byELISA.RESULTS:1. The percentage of the CD4+CD25+ T cells in the marrow and spleen fromasthmatic model group were significantly higher than those from normal controlgroup and model control group (P<0.05), then those from mIL-12 plamidprevention group and mIL-12 plasmid treatment group showed significantlydecrease compared with those from asthmatic model group (PO.05).2.The levels of TGF- 0 ,IL-4 and IL-5 in the bronchoalveolar lavage fluids (BALF)changes consistently with the percentage of the CD4+CD25+ T cells in the spleen.3.The percentage of the CD4+CD25+ T cells in peripheral blood and the levels ofIL-10 and TGF- P in the serum were showed no distinctly difference.CONCLUSION:CD4+CD25+ T cells and the associated cytokines are tightly correlated with the pathogenisis of asthma, intramuscularly administration of mIL-12 plasmid can obviously influence the percentage of CD4+CD25+ T cells from mouse asthmatic models, so we confer that the mechanism of asthma treatment with mIL-12 plasmid may partly relate to CD4+CD25+ T cells.