Sone S, Nishioka Y, Nii A, Yanagawa H, Orino E, Mizuno K, Yano S, Ogura T
Third Department of Internal Medicine, University of Tokushima School of Medicine, Japan.
Nihon Kyobu Shikkan Gakkai Zasshi. 1992 Dec;30 Suppl:207-12.
The present study was undertaken to examine the effects of IL-4 on induction of cytotoxic killer activity and on production of antitumor mediators by human monocytes and alveolar macrophages (AM). The spontaneous tumoricidal activity of AM was slightly suppressed by IL-4. Addition of IL-4 to cultures of AM or monocytes with endotoxin resulted in dose-dependent suppression of their cytotoxic activity against A375 and its variant cells resistant to IL-1 and TNF-alpha. IL-4 inhibited the production of IL-1 and TNF-alpha by AM at the protein and mRNA levels. Oxygen radical production was also suppressed by treating AM with IL-4. IL-1 receptor antagonist (IL-1ra) was also produced by monocytes stimulated with LPS, but not with IL-4. Marked up-regulation by IL-4 of IL-1ra production in LPS-stimulated monocytes was observed at both the mRNA and protein levels. These findings suggest that IL-4 may be important in down-regulation of antitumor activation of human monocyte-macrophages, not only directly through inhibition of production of antitumor effector molecules, but also indirectly through up-regulation of production of IL-1ra.
本研究旨在探讨白细胞介素-4（IL-4）对人单核细胞和肺泡巨噬细胞（AM）诱导细胞毒性杀伤活性以及抗肿瘤介质产生的影响。IL-4轻微抑制了AM的自发杀瘤活性。将IL-4添加到AM或单核细胞与内毒素的培养物中，会导致它们对A375及其对IL-1和肿瘤坏死因子-α（TNF-α）耐药的变异细胞的细胞毒性活性呈剂量依赖性抑制。IL-4在蛋白质和mRNA水平上抑制了AM产生IL-1和TNF-α。用IL-4处理AM也会抑制氧自由基的产生。脂多糖（LPS）刺激的单核细胞会产生白细胞介素-1受体拮抗剂（IL-1ra），但IL-4刺激的单核细胞不会产生。在mRNA和蛋白质水平上均观察到，IL-4可显著上调LPS刺激的单核细胞中IL-1ra的产生。这些发现表明，IL-4可能在下调人单核细胞-巨噬细胞的抗肿瘤激活中起重要作用，不仅直接通过抑制抗肿瘤效应分子的产生，还间接通过上调IL-1ra的产生。
