免疫刺激DNA序列与过敏原联用对哮喘小鼠模型气道过敏性炎症的作用

目的　观察免疫刺激DNA序列 (ISS DNA)单用和与过敏原卵白蛋白 (OVA)合用 ,对支气管哮喘 (简称哮喘 )小鼠模型气道过敏性炎症的作用及作用维持时间。方法　BALB/c小鼠 36只 ,分ISS组 (A组 ) 12只、ISS +OVA组 (B组 ) 12只、OVA组 (C组 ) 6只和生理盐水 (NS)组 (D组 ) 6只。A、B、C组用OVA致敏及激发。A组和B组根据注射次数再分A1、B11次注射组 (1次腹腔注射ISS DNA 10 0μg或ISS DNA 10 0 μg +OVA 10 μg)和A2 、B2 2次注射组 (2次腹腔注射ISS DNA或ISS DNA +OVA)。各组在第 1次激发后 6周中 ,每周采血 1次测特异性IgE ,最后处死小鼠测支气管肺泡灌洗液 (BALF)中细胞计数及分类 ,肺组织病理检查 ,检测脾细胞分泌γ干扰素 (IFN γ)的水平。结果　BALF中嗜酸细胞 (EOS)数A1组为 (2 39± 0 81)× 10 4/ml;A2 组为 (2 .6 2± 0 .77)× 10 4/ml;B1组为 (1.80± 0 .12 )× 10 4/ml;B2 组为 (1.84± 0 .6 7)× 10 4/ml,与C组 (12 .4 3± 2 .13)× 10 4/ml]比较差异有显著性 (P <0 .0 5 )。脾细胞分泌的IFN γA1组为 (5 10± 10 2 )pg/ml;A2 组为 (492± 98)pg/ml;B1组为 (5 32± 12 0 )pg/ml;B2组为 (46 9± 132 )pg/ml,与C组 (194± 80 )pg/ml]比较差异有显著性 (P <0 .0 5 )。血清IgE前 4周B组与C组比较

Modulation of allergic airway inflammation by immunostimulatory DNA sequences in conjunction with an allergen in a murine model of asthma

OBJECTIVE: To compare the suppressive effects of immunostimulatory sequences (ISS-DNA) alone or ISS-DNA in conjunction with ovalbumin (OVA) on airway inflammation in a mouse model of asthma. METHODS: Thirty six female BALB/c mice were divided into 4 groups: group ISS (A), group ISS + OVA (B), group OVA (C) and group normal saline (D). Mice in groups A, B and C were sensitized and challenged with OVA. Group A and group B were subdivided into subgroup A(1) and B(1) (injected intraperitoneally with ISS DNA 100 micro g or ISS DNA 100 micro g and OVA 10 micro g once) and subgroup A(2) and B(2) (injected intraperitoneally with ISS DNA or ISS DNA and OVA twice). Blood samples were obtained every week for six weeks. OVA-specific IgE was measured by ELISA. Bronchoalveolar lavage fluid (BALF), lung tissues and spleen cells were collected. BAL total cell numbers and differentials were counted. Interferon gamma (IFN-gamma) produced by OVA-stimulated spleen cells was determined by ELISA. RESULTS: Eosinophil count in group A(1) (2.39 +/- 0.81) x 10(4)/ml], group A(2) (2.62 +/- 0.77) x 10(4)/ml], group B(1) (1.80 +/- 0.12) x 10(4)/ml], and group B(2) (1.84 +/- 0.67) x 10(4)/ml] were significantly lower than those in group C (12.43 +/- 2.13) x 10(4)/ml], P < 0.05. The levels of IFN-gamma in group A(1) (510 +/- 102) pg/ml], group A(2) (492 +/- 98) pg/ml], group B(1) (532 +/- 120) pg/ml], and group B(2) (469 +/- 132) pg/ml] were significantly higher than those in group C (194 +/- 80) pg/ml], P < 0.05. The serum level of IgE in group B was significantly lower than that in group C in four weeks, but that in group A was not significantly different from that in group C. A second dose of ISS-DNA did not show additional effect as compared to the signal dose treatment. CONCLUSIONS: ISS-DNA inhibited allergic airway inflammation in a murine model of asthma. ISS-DNA and OVA combination was more effective than ISS-DNA alone.