Interleukin 10 (IL-10) Inhibits Human Lymphocyte Interferon 3,-Production by Suppressing Natural Killer Cell Stimulatory Factor/IL-12 Synthesis in Accessory Cells By Annalisa D'Andrea, Miguel Aste-Amezaga,
Interleukin 10 (IL-10) Inhibits Human Lymphocyte Interferon 3,-Production by Suppressing Natural Killer Cell Stimulatory Factor/IL-12 Synthesis in Accessory Cells By Annalisa D'Andrea, Miguel Aste-Amezaga,
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发表时间：
1993
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通讯作者：
N. Valiante;Xiaojing Ma;M. Kubin;G. Trinchieri
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作者：
N. Valiante;Xiaojing Ma;M. Kubin;G. Trinchieri
硫自然杀伤细胞刺激因子或白细胞介素 12 (NKSF/IL-12) 是一种异二聚体细胞因子，由单核细胞/巨噬细胞、B 细胞和可能的其他辅助细胞类型产生，主要响应细菌或细菌产物。 NKSF/IL-12 介导 T 和 NK 细胞的多形性生物活性，单独或与其他诱导剂协同作用，是干扰素 3' (IFN-3") 产生的强大刺激剂。IL-10 是单核细胞巨噬细胞活化的有效抑制剂，可抑制在辅助细胞水平发挥作用的淋巴细胞产生肿瘤坏死因子 ot（TNF-o 0、IL-1 和 IFN-3'）。 TNF-ot 和 IL-1 不是 IFN-3' 的有效诱导剂，IL-10 抑制 IFN-3' 产生的机制尚不清楚。在本文中，我们表明 IL-10 是金黄色葡萄球菌或脂多糖 (LPS) 激活的人外周血单核细胞产生 NKSF/IL-12 的有效抑制剂，同时抑制游离 NKSF/IL-12 p40 链的产生。 p70异二聚体被IL-10阻断 p40链mRNA积累被金黄色葡萄球菌或LPS强烈诱导并被IL-10下调，而p35 mRNA持续表达并且仅受金黄色葡萄球菌、LPS或IL-10最低程度的调节，尽管IL-10能够阻断NKSF/IL-12(IFN-3'的强大诱导剂)的产生。在体外和体内，IL-10抑制IFN-3'的机制不能仅仅根据NKSF/IL-12的抑制来解释，因为IL-10可以部分抑制NKSF/IL-12诱导的IFN-3'产生，而且，在NKSF/IL-12中和抗体存在下响应各种刺激的IFN-3'产生。 IL-1~可显着抑制响应各种刺激的IFN-3’产生，并且NKSF/IL-12和IL-1B可以克服IL-10介导的IFN-%抑制，表明IL-10对IFN-3’产生的抑制主要是由于其阻断辅助细胞的IFN-3’诱导剂NKSF/IL12以及共刺激分子IL-1/~的产生。
SulTlnlary Natural killer cell stimulatory factor or interleukin 12 (NKSF/IL-12) is a heterodimeric cytokine produced by monocytes/macrophages, B cells, and possibly other accessory cell types primarily in response to bacteria or bacterial products. NKSF/IL-12 mediates pleiomorphic biological activity on T and NK cells and, alone or in synergy with other inducers, is a powerful stimulator of interferon 3' (IFN-3") production. IL-10 is a potent inhibitor of monocyte-macrophage activation, that inhibits production of tumor necrosis factor ot (TNF-o 0, IL-1 and also IFN-3' from lymphocytes acting at the level of accessory cells. Because TNF-ot and IL-1 are not efficient inducers of IFN-3', the mechanism by which IL-10 inhibits IFN-3' production is not clear. In this paper, we show that IL-IO is a potent inhibitor of NKSF/IL-12 production from human peripheral blood mononuclear cells activated with Staphylococcus aureus or lipopolysaccharide (LPS). Both the production of the free NKSF/IL-12 p40 chain and the biologically active p70 heterodimer are blocked by IL-10. NKSF/IL-12 p40 chain mRNA accumulation is strongly induced by S. aureus or LPS and downregulated by IL-10, whereas the p35 mRNA is constitutively expressed and only minimally regulated by S. aureus, LPS, or IL-10. Although IL-IO is able to block the production of NKSF/IL-12, a powerful inducer of IFN-3' both in vitro and in vivo, the mechanism of inhibition of IFN-3' by IL-10 cannot be explained only on the basis of inhibition of NKSF/IL-12 because IL-10 can partially inhibit IFN-3' production induced by NKSF/IL-12, and also, the IFN-3' production in response to various stimuli in the presence of neutralizing antibodies to NKSF/IL12. Our findings that antibodies against NKSF/IL-12, TNF-o~, or IL-1~ can significantly inhibit IFN-3" production in response to various stimuli and that NKSF/IL-12 and IL-1B can overcome the IL-10-mediated inhibition of IFN-% suggest that IL-10 inhibition of IFN-3' production is primarily due to its blocking production from accessory cells of the IFN-3'-inducer NKSF/IL12, as well as the costimulating molecule IL-1/~.