[免疫刺激DNA序列联合变应原对哮喘小鼠模型变应性气道炎症的调节作用]

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

作者信息

Jin Meiling, Cai Yingyun, Yuan Zhenghong, Zheng Lingjie, Ren Tao

机构信息

Department of Respiratory Disease, Zhongshan Hospital, Fudan University, Shanghai 200032, China.

出版信息

Zhonghua Jie He He Hu Xi Za Zhi. 2002 Sep;25(9):542-5.

PMID:12423563

Abstract

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.

摘要

目的

比较免疫刺激序列（ISS-DNA）单独使用或与卵清蛋白（OVA）联合使用对哮喘小鼠模型气道炎症的抑制作用。

方法

将36只雌性BALB/c小鼠分为4组：ISS组（A组）、ISS + OVA组（B组）、OVA组（C组）和生理盐水组（D组）。A、B、C组小鼠用OVA致敏并激发。A组和B组再分为A(1)亚组和B(1)亚组（腹腔注射100μg ISS DNA或100μg ISS DNA加10μg OVA一次）以及A(2)亚组和B(2)亚组（腹腔注射ISS DNA或ISS DNA加OVA两次）。连续六周每周采集血样。通过ELISA法检测OVA特异性IgE。收集支气管肺泡灌洗液（BALF）、肺组织和脾细胞。计数BAL总细胞数及分类。通过ELISA法测定OVA刺激的脾细胞产生的干扰素γ（IFN-γ）。

结果

A(1)组[（2.39±0.81）×10⁴/ml]、A(2)组[（2.62±0.77）×10⁴/ml]、B(1)组[（1.80±0.12）×10⁴/ml]和B(2)组[（1.84±0.67）×10⁴/ml]的嗜酸性粒细胞计数显著低于C组[（12.43±2.13）×10⁴/ml]，P<0.05。A(1)组[（510±102）pg/ml]、A(2)组[（492±98）pg/ml]、B(1)组[（532±120）pg/ml]和B(2)组[（469±132）pg/ml]的IFN-γ水平显著高于C组[（194±80）pg/ml]，P<0.05。B组血清IgE水平在四周时显著低于C组，但A组与C组无显著差异。与单次剂量治疗相比，第二次注射ISS-DNA未显示出额外效果。