Impaired interleukin 12 production in human immunodeficiency virus-infected patients.

Impaired interleukin 12 production in human immunodeficiency virus-infected patients.
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DOI:
10.1084/jem.179.4.1361
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发表时间:
1994-04-01
影响因子:
15.3
通讯作者:
Trinchieri, G
Trinchieri, G
中科院分区:
医学1区
文献类型:
--
作者:
Chehimi, J;Starr, S E;Frank, I;D'Andrea, A;Ma, X;MacGregor, R R;Sennelier, J;Trinchieri, G

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当在体外用常见的人类病原体金黄色葡萄球菌进行攻击时,来自人类免疫缺陷病毒(HIV)感染患者(无症状或患有获得性免疫缺陷病毒)的外周血单核细胞(PBMC)产生的白细胞介素12(IL-12)游离重链和生物活性IL-12异二聚体比来自未感染健康供体的PBMC低10倍。相比之下,来自HIV感染个体和未感染对照供体的PBMC产生相似水平的肿瘤坏死因子α、IL-1 β和IL-10,并且来自HIV感染个体的PBMC产生的IL-6是来自未感染对照供体的PBMC的3 - 4倍。IL-12产生的缺陷不是由于IL-10的过度产生,IL-10是一种对IL-12产生自分泌负反馈的细胞因子,而是与HIV感染直接相关,如体外感染HIV的单核细胞产生IL-12的能力降低所表明的。IL-12缺乏可能是HIV感染相关免疫缺陷的重要组成部分。
Peripheral blood mononuclear cells (PBMC) from human immunodeficiency virus (HIV)-infected patients, asymptomatic or with acquired immunodeficiency virus, produced 10-fold less interleukin 12 (IL-12) free heavy chain and fivefold less biologically active IL-12 heterodimer than PBMC from uninfected healthy donors when challenged in vitro with the common human pathogen Staphylococcus aureus. In contrast, PBMC from HIV-infected individuals and uninfected control donors produced similar levels of tumor necrosis factor alpha, IL-1 beta, and IL-10, and PBMC from HIV-infected individuals produced three- to fourfold more IL-6 compared with PBMC from uninfected control donors. The defect in IL-12 production is not due to hyperproduction of IL-10, a cytokine exerting an autocrine-negative feedback on IL-12 production, but was directly related to HIV infection, as suggested by the reduced ability of monocytes infected in vitro with HIV to produce IL-12. IL-12 deficiency may be an important component of the immunodeficiency associated with HIV infection.