In vitro responsiveness to IL-18 in combination with IL-12 or IL-2 by PBMC from patients with bronchial asthma and atopic dermatitis
In vitro responsiveness to IL-18 in combination with IL-12 or IL-2 by PBMC from patients with bronchial asthma and atopic dermatitis
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DOI：
10.1016/j.clim.2003.12.006
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发表时间：
2004-04-01
影响因子：
8.6
通讯作者：
Matsumoto, T
中科院分区：
文献类型：
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作者：
El-Mezayen, REH;Matsumoto, T
白介素18(IL-18)是一种促炎细胞因子，目前被认为是辅助性T细胞(Th)1和2细胞因子产生的重要调节因子。据报道，过敏性疾病患者的IL-18分泌增加。它主要由激活的巨噬细胞产生，并与IL-12和IL-2协同诱导干扰素-γ的合成，从而促进Th1细胞因子的应答。矛盾的是，IL-18本身强烈地诱导免疫球蛋白(Ig)E和过敏性炎症，表明IL-18在促进Th2反应中发挥作用。研究了IL-18与II-12或II-2联合应用对变态反应性疾病患者外周血单个核细胞(PBMC)产生Th1/Th2型细胞因子的诱导作用。用植物血凝素(PHA)和IL-12或IL-2联合培养44例过敏性疾病患者(23例支气管哮喘(BA)和21例特应性皮炎(AD))和20例健康对照的PBMC。用酶免疫分析法检测培养上清液中的干扰素-γ、IL-13和IL-4水平。在IL-12存在的情况下，用IL-18刺激的非过敏对照组的所有培养物中都能检测到干扰素-γ的产生；然而，5名BA患者和5名AD患者的结果低于干扰素-γ的检测下限。在IL-2的协同作用下，IL-18能够诱导所有非过敏性对照组和所有过敏性患者的PBMC产生干扰素-γ，但一名AD患者除外。IL-18+IL-2可协同诱导IL-13的产生，BA患者的IL-13诱生水平明显高于非过敏对照组(P=0.006)。IL-18的刺激，即使与IL-2结合，也不能诱导非过敏性对照和过敏性患者的PBMC产生IL-4。尽管约1/4的过敏症患者IL-18+IL-12对干扰素-γ的诱导作用受损，但在IL-18存在的情况下，IL-2可完全恢复干扰素-γ的产生。提示IL-18/IL-12/IL-2途径参与了Th1/Th2细胞因子反应的调节，IL-18/IL-12/IL-2途径参与了Th1/Th2细胞因子的调节。(C)2004 Elsevier Inc.保留所有权利。
Interleukin (IL)-18 is a proinflammatory cytokine and is now recognized as an important regulator of both helper T cells (Th) 1 and 2 cytokine production. An increased IL-18 secretion has been reported in patients with allergic disorders. It is predominantly produced by activated macrophages, and synergizes with IL-12 and IL-2 to induce IFN-gamma synthesis, thereby promoting Th1 cytokine response. Paradoxically, IL-18, by itself, strongly induces immunoglobulin (Ig) E and allergic inflammation, indicating a role for IL-18 in promoting Th2 response. We investigated the inducing effect in vitro of combining IL-18 and II-12 or II-2 on Th1- and Th2-type cytokines production by peripheral blood mononuclear cells (PBMC) from patients with allergic diseases. PBMC derived from 44 allergic patients (23 bronchial asthma (BA) and 21 atopic dermatitis (AD)] and 20 healthy controls were cultured with IL-18 in the presence of phytohemagglutinin (PHA) and IL-12 or IL-2. The levels of IFN-gamma, IL-13, and IL-4 in the culture supernatants were measured using enzymatic immunoassaying. IFN-gamma production was detected in all cultures from nonallergic controls stimulated with IL-18 in the presence of IL-12; however, the results for five BA patients and five AD patients were under the detection limit for IFN-gamma. In collaboration with IL-2, IL-18 was able to induce IFN-gamma production by PBMCs from all nonallergic controls and all allergic patients, with the exception of one AD patient. Synergistic induction of IL-13 production was found in cultures with TL-18 + IL-2, and the IL-13 induction was significantly increased in BA patients when compared with that in nonallergic controls (P = 0.006). The stimulation by IL- 18, even in combination with IL-2, failed to induce IL-4 production by PBMC from both nonallergic controls and allergic patients. Although the induction of IFN-gamma by IL-18 + IL-12 was impaired in around a quarter of the allergic patients, the impairment of the IFN-gamma production was completely restored by IL-2 in the presence of IL-18. Thus, IL-18 enhances IFN-gamma production through an IL-12-dependent pathway and exhibits synergism when combined with IL-2 in terms of enhanced IL-13 and IFN-gamma production, suggesting the involvement of IL-18/IL-12/IL-2 pathway in modulating Th1/Th2 cytokine response. (C) 2004 Elsevier Inc. All rights reserved.