Interleukin-11 modulates Th1/Th2 cytokine production from activated CD4+ T cells
Interleukin-11 modulates Th1/Th2 cytokine production from activated CD4+ T cells
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DOI：
10.1089/107999001459123
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发表时间：
2001-01-01
影响因子：
2.3
通讯作者：
Trepicchio, WL
中科院分区：
文献类型：
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作者：
Bozza, M;Bliss, JL;Trepicchio, WL
重组人白细胞介素-11（rHuIL-11）是一种多效性细胞因子，对多种细胞类型具有作用。rHuIL-11降低活化的巨噬细胞活性并下调促炎介质如肿瘤坏死因子-α（TNF-α）和一氧化氮（NO）的产生。在体外和体内，rHuIL-11抑制关键免疫刺激细胞因子的产生，包括IL-12和干扰素-γ（IFN-γ）。rHuIL-11最近在人银屑病临床试验中显示出下调IFN-γ产生、增加IL-4产生和减少炎性组织损伤的免疫调节活性。这些影响的细胞机制尚未完全阐明。我们在此证明，在人和鼠CD 4（+）和CD 8（+）淋巴细胞中检测到gp 130和IL-11受体（IL-11 R）α mRNA（IL-11 R复合物的组分）的表达，表明rHuIL-11可以直接与T细胞相互作用。在鼠T细胞分化的细胞培养模型中，rHuIL-11用于抑制IL-2产生以及IL-12诱导的IFN-γ产生，并增强IL-4和IL-10产生。rHuIL-11对T细胞增殖无影响。rHuIL-11调节活化的CD 4（+）T细胞产生细胞因子的能力提供了一种机制，通过该机制，rHuIL-11可以改善银屑病等炎性疾病。
Recombinant human interleukin-11 (rHuIL-11) is a pleiotropic cytokine with effects on multiple cell types. rHuIL-11 reduces activated macrophage activity and downregulates production of proinflammatory mediators, such as tumor necrosis factor-alpha (TNF-alpha) and nitric oxide (NO). In vitro and in vivo, rHuIL-11 inhibits production of key immunostimulatory cytokines, including IL-12 and interferon-gamma (IFN-gamma). rHuIL-11 has recently demonstrated immunomodulatory activity to downregulate IFN-gamma production, increase IL-4 production, and reduce inflammatory tissue injury in a human psoriasis clinical trial. The cellular mechanisms of these effects are not fully elucidated. We demonstrate here that expression of gp130 and IL-11 receptor (IL-11R) alpha mRNA, components of the IL-11R complex, are detected in human and murine CD4(+) and CD8(+) lymphocytes, suggesting that rHuIL-11 can directly interact with T cells. In a cell culture model of murine T cell differentiation, rHuIL-11 acts to inhibit IL-2 production as well as IL-12-induced IFN-gamma production and enhances IL-4 and IL-10 production. rHuIL-11 had no effect on T cell proliferation. The ability of rHuIL-11 to modulate cytokine production from activated CD4(+) T cells provides a mechanism through which rHuIL-11 may ameliorate such inflammatory diseases as psoriasis.