Cytokine-directed therapies in asthma

Cytokine-directed therapies in asthma
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哮喘的细胞因子导向疗法

DOI:
10.1046/j.1440-1592.2003.00287.x
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发表时间:
2003
影响因子:
6.8
通讯作者:
P. Barnes
P. Barnes
中科院分区:
医学2区
文献类型:
--
作者:
P. Barnes

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多种细胞因子在哮喘炎症的协调和持续中发挥着关键作用,目前正在开发几种特定的细胞因子和趋化因子抑制剂作为未来的治疗方法。抗白细胞介素 (IL)-5 抗体可显着减少外周血和气道嗜酸性粒细胞,但似乎对症状性哮喘无效。尽管 IL-4 的抑制在治疗哮喘方面具有良好的早期效果,但已被停止,而阻断 IL-13 可能更有效。抑制性细胞因子,如 IL-10、干扰素和 IL-12 前景不太乐观,因为全身给药会产生副作用。抑制肿瘤坏死因子 (TNF)-α 可能有助于治疗严重哮喘。许多趋化因子参与哮喘的炎症反应,并且几种趋化因子受体的小分子抑制剂正在开发中。 CCR3 拮抗剂(阻断嗜酸性粒细胞趋化性)正处于治疗哮喘的临床开发阶段。由于哮喘涉及多种细胞因子,因此抑制多种细胞因子合成的药物可能更有用。几种此类药物目前正处于临床开发阶段,这些非特异性抑制剂的任何副作用风险都可以通过吸入途径降低。
Multiple cytokines play a critical role in orchestrating and perpetuating inflammation in asthma and several specific cytokine and chemokine inhibitors are now in development as future therapy. Anti-interleukin (IL)-5 antibodies markedly reduce peripheral blood and airway eosinophils, but do not appear to be effective in symptomatic asthma. Inhibition of IL-4, despite promising early results in asthma, has been discontinued and blocking IL-13 may be more effective. Inhibitory cytokines, such as IL-10, interferons and IL-12 are less promising, because systemic delivery produces side-effects. Inhibition of tumor necrosis factor (TNF)-α may be useful in severe asthma. Many chemokines are involved in the inflammatory response of asthma and several small molecule inhibitors of chemokine receptors are in development. The CCR3 antagonists (which block eosinophil chemotaxis) are in clinical development for asthma. Because so many cytokines are involved in asthma, drugs that inhibit the synthesis of multiple cytokines may prove to be more useful; several such classes of drug are now in clinical development and any risk of side-effects with these non-specific inhibitors may be reduced by the inhaled route.
单核细胞趋化蛋白-1 介导正常小鼠而非 CCR2-/- 小鼠中蟑螂过敏原诱导的支气管高反应性:肥大细胞的作用。
DOI: --
发表时间: 1999
期刊: Journal of immunology (Baltimore, Md. : 1950)
影响因子: --
作者:
Campbell,EM;Charo,IF;Kunkel,SL;Strieter,RM;Boring,L;Gosling,J;Lukacs,NW
通讯作者: Lukacs,NW
DOI: 10.1067/mai.2002.127512
发表时间: 2002-09-01
影响因子: 14.2
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通讯作者: Umetsu, DT
DOI: 10.1164/ajrccm.160.6.9808146
发表时间: 1999-12-01
影响因子: 24.7
作者:
Borish, LC;Nelson, HS;Garrison, L
通讯作者: Garrison, L
DOI: 10.1164/ajrccm.156.3.9610046
发表时间: 1997-09-01
影响因子: 24.7
作者:
Wenzel, SE;Szefler, SJ;Martin, RJ
通讯作者: Martin, RJ
DOI: 10.1016/s0002-9440(10)62562-x
发表时间: 2002-04-01
影响因子: 6
作者:
Lukacs, NW;Berlin, A;Bridger, GJ
通讯作者: Bridger, GJ