Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides.

Long term prevention of allergic lung inflammation in a mouse model of asthma by CpG oligodeoxynucleotides.
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通过 CpG 寡脱氧核苷酸长期预防哮喘小鼠模型中的过敏性肺部炎症。

DOI:
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发表时间:
1999
影响因子:
4.4
通讯作者:
Dennis M. Klinman
Dennis M. Klinman
中科院分区:
医学2区
文献类型:
--
作者:
S. Sur;J. Wild;B. Choudhury;N. Sur;Rafeul Alam;Dennis M. Klinman

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哮喘是一种由Th2细胞因子诱导、Th1细胞因子抑制的气道炎症性疾病。尽管哮喘的发病率、发病率和死亡率稳步上升,但目前的治疗方法无法长期减少或预防哮喘。我们检查了非甲基化 CpG 寡脱氧核苷酸 (ODN) 的能力,它是 Th1 细胞因子的有效诱导剂,可预防对豚草过敏原敏感的小鼠的哮喘炎症和生理表现。在过敏原攻击前 48 小时施用 CpG ODN 可增加 IFN-γ 与 IL-4 分泌细胞的比率,减少过敏原诱导的嗜酸性粒细胞募集,并减少豚草过敏原特异性 IgE 产生细胞的数量。 CpG ODN 的这些作用在施用后持续至少 6 周。此外,在施用 CpG ODN 后 6 周,Th1 对记忆 Ag 的记忆反应强烈,抑制了支气管周围和血管周围的肺部炎症,并抑制了支气管高反应性。在 IFN-gamma -/- 小鼠中施用 CpG ODN 未能抑制嗜酸性粒细胞的募集,表明 IFN-gamma 在介导这些作用中发挥着关键作用。这是第一份关于长期抑制预致敏动物过敏性肺部炎症的治疗方法的报告,因此与开发有效的哮喘长期治疗方法相关。
Asthma is an inflammatory disease of the airways that is induced by Th2 cytokines and inhibited by Th1 cytokines. Despite a steady increase in the incidence, morbidity, and mortality from asthma, no current treatment can reduce or prevent asthma for a prolonged period. We examined the ability of unmethylated CpG oligodeoxynucleotides (ODN), which are potent inducers of Th1 cytokines, to prevent the inflammatory and physiological manifestations of asthma in mice sensitized to ragweed allergen. Administration of CpG ODN 48 h before allergen challenge increased the ratio of IFN-gamma to IL-4 secreting cells, diminished allergen-induced eosinophil recruitment, and decreased the number of ragweed allergen-specific IgE-producing cells. These effects of CpG ODN were sustained for at least 6 wk after its administration. Furthermore, there was a vigorous Th1 memory response to the recall Ag, inhibition of peribronchial and perivascular lung inflammation, and inhibition of bronchial hyperresponsiveness 6 wk after administration of CpG ODN. Administration of CpG ODN in IFN-gamma -/- mice failed to inhibit eosinophil recruitment, indicating a critical role of IFN-gamma in mediating these effects. This is the first report of a treatment that inhibits allergic lung inflammation in presensitized animals for a prolonged period and thus has relevance to the development of an effective long term treatment for asthma.
DOI: --
发表时间: 1998
影响因子: 4.4
作者:
J. Kline;T. Waldschmidt;T. Businga;J. E. Lemish;J. Weinstock;P. Thorne;A. Krieg
通讯作者: J. Kline;T. Waldschmidt;T. Businga;J. E. Lemish;J. Weinstock;P. Thorne;A. Krieg
DOI: 10.1164/ajrccm.156.3.9606031
发表时间: 1997-09-01
影响因子: 24.7
作者:
Hamelmann, E;Schwarze, J;Gelfand, EW
通讯作者: Gelfand, EW
过敏原攻击后 24 小时,嗜酸性粒细胞募集与 IL-5 相关,但与 RANTES 无关。
DOI: 10.1016/s0091-6749(96)70195-1
发表时间: 1996
期刊: The Journal of allergy and clinical immunology
影响因子: --
作者:
Sur,S;Kita,H;Gleich,GJ;Chenier,TC;Hunt,LW
通讯作者: Hunt,LW
DOI: 10.1073/pnas.93.7.2879
发表时间: 1996-04-02
影响因子: 11.1
作者:
Klinman, DM;Yi, AK;Krieg, AM
通讯作者: Krieg, AM
DOI: 10.4049/jimmunol.161.12.7054
发表时间: 1998-12
影响因子: 4.4
作者:
D. Broide;J. Schwarze;H. Tighe;Tim Gifford;M. Nguyen;S. Malek;J. V. Van Uden;E. Martín-Orozco;E. Gelfand;E. Raz
通讯作者: D. Broide;J. Schwarze;H. Tighe;Tim Gifford;M. Nguyen;S. Malek;J. V. Van Uden;E. Martín-Orozco;E. Gelfand;E. Raz