Mangan D F, Robertson B, Wahl S M
Cellular Immunology Section, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892.
J Immunol. 1992 Mar 15;148(6):1812-6.
Because IL-4 down-regulates several proinflammatory functions associated with human monocytes/macrophages, we explored the possibility that IL-4 also decreases monocyte survival. IL-4 caused a concentration-dependent decrease in viability of IL-1 or LPS stimulated, but not unstimulated, monocytes. Nonviable cells demonstrated classic features of programmed cell death or apoptosis, in that they were condensed and contained oligonucleosome-sized (200 bp) DNA fragments. When compared with several other cytokines commonly associated with inflammatory lesions, IL-4 was uniquely effective in enhancing cell death. We found that IL-4 enhanced death more quickly in IL-1-stimulated cells than in LPS-stimulated cells, that stimulated monocytes did not become resistant to the effects of IL-4 during culture, and that the effects of IL-4 on viability were antagonized by IFN-gamma. Enhanced cell death was stimulus-specific in that monocyte viability maintained by certain activating agents, such as Con A or CSF, was unaffected by IL-4. These findings represent the first evidence of cytokine-enhanced programmed cell death in monocytes and suggest that the antiinflammatory effects of IL-4 are mediated in part by reducing survival of stimulated monocytes in chronic lesions.
由于白细胞介素-4（IL-4）可下调与人类单核细胞/巨噬细胞相关的多种促炎功能，我们探究了IL-4是否也会降低单核细胞的存活率。IL-4导致经白细胞介素-1（IL-1）或脂多糖（LPS）刺激而非未经刺激的单核细胞活力呈浓度依赖性降低。无活力的细胞表现出程序性细胞死亡或凋亡的典型特征，即细胞浓缩并含有寡核小体大小（200 bp）的DNA片段。与通常与炎症病变相关的其他几种细胞因子相比，IL-4在增强细胞死亡方面具有独特的效果。我们发现，IL-4在IL-1刺激的细胞中比在LPS刺激的细胞中更快地增强细胞死亡，在培养过程中，受刺激的单核细胞不会对IL-4的作用产生抗性，并且IL-4对活力的影响可被γ干扰素（IFN-γ）拮抗。增强的细胞死亡具有刺激特异性，因为某些激活剂（如刀豆蛋白A或集落刺激因子）维持的单核细胞活力不受IL-4影响。这些发现代表了细胞因子增强单核细胞程序性细胞死亡的首个证据，并表明IL-4的抗炎作用部分是通过降低慢性病变中受刺激单核细胞的存活率来介导的。
