Priming with IL-4 and IL-13 during HIV-1 infection restores in vitro IL-12 production by mononuclear cells of HIV-infected patients.
Priming with IL-4 and IL-13 during HIV-1 infection restores in vitro IL-12 production by mononuclear cells of HIV-infected patients.
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DOI：
10.4049/jimmunol.159.11.5705
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发表时间：
1997-12
影响因子：
4.4
通讯作者：
J. Marshall;S. Robertson;G. Trinchieri;J. Chehimi
中科院分区：
文献类型：
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作者：
J. Marshall;S. Robertson;G. Trinchieri;J. Chehimi
促炎性细胞因子的产生可以由几种发挥激活或抑制作用的因素调节。IL-4、IL-10、IL-13、TGF-β和PGE 2已经证明了非常广泛的有效的巨噬细胞失活活性，特别是下调许多促炎性单核因子的产生。IL-12通过提供天然抗性和适应性免疫之间的联系在免疫应答期间起关键作用。我们和其他人以前已经表明，在IL-12的生产从HIV-1感染者的PBMC响应于各种刺激的损害，但定义的机制负责仍然难以捉摸。在这项研究中，我们观察到，从患者的PBMC与IL-4或IL-13的预处理24小时启动的细胞增强生产的IL-12响应于金黄色葡萄球菌，几乎完全恢复其不足的IL-12生产时，与健康对照组相比。尽管IL-10和PGE 2完全消除了这种引发作用，但来自患者和对照的未经处理的和IL-4或IL-13预处理的PBMC产生的IL-10相当。此外，阻断PGE 2合成的吲哚美辛和cAMP阻断剂未能恢复或增强IL-12的产生。IL-4和IL-13对p40和p35基因的引发作用均在转录水平。鉴于IL-12和IL-4在促进Th 1或Th 2免疫反应中的相互拮抗作用，Th 2相关细胞因子对IL-12产生的完全恢复是出乎意料的。
The production of proinflammatory cytokines can be regulated by several factors that exert activating or inhibitory effects. IL-4, IL-10, IL-13, TGF-beta, and PGE2 have demonstrated a very wide range of potent macrophage-deactivating activities and, specifically, down-regulation of the production of many proinflammatory monokines. IL-12 plays a key role during immune response by providing a link between natural resistance and adaptive immunity. We and others have previously shown an impairment in IL-12 production by PBMC from HIV-1-infected individuals in response to various stimuli, but defining the mechanism responsible remains elusive. In this study, we observed that pretreatment of PBMC from patients with IL-4 or IL-13 for 24 h primes the cells for enhanced production of IL-12 in response to Staphylococcus aureus, and almost completely restores their deficient IL-12 production when compared with healthy controls. Although this priming effect was completely abrogated by IL-10 and PGE2, IL-10 was produced equivalently by untreated and IL-4- or IL-13-pretreated PBMC from both patients and controls. Additionally, indomethacin, which shuts off PGE2 synthesis, and cAMP-blocking reagents failed to restore or enhance IL-12 production. The priming effect of IL-4 and IL-13 is at the transcription level for both p40 and p35 genes. This complete restoration of IL-12 production by Th2-associated cytokines was unexpected in light of the mutually antagonistic roles of IL-12 and IL-4 in promoting Th1 or Th2 immune responses.