Standiford T J, Strieter R M, Chensue S W, Westwick J, Kasahara K, Kunkel S L
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109-0602.
J Immunol. 1990 Sep 1;145(5):1435-9.
Peripheral blood monocytes are important mediators of inflammation via the generation of various bioactive substances, including the recently isolated and cloned chemotactic peptide IL-8. Through cytokine networking, monocyte-derived cytokines are capable of inducing IL-8 expression from non-immune cells. IL-4, a B and T lymphocyte stimulatory factor, has recently been shown to inhibit monocyte/macrophage function, including the ability to suppress monocyte-generated cytokines. We describe the in vitro inhibition of IL-8 gene expression and synthesis from LPS, TNF, and IL-1 stimulated peripheral blood monocytes by IL-4. IL-4 suppressed IL-8 production from stimulated monocytes in a dose-dependent fashion, with partial suppression observed at IL-4 concentrations as low as 10 pg/ml. The IL-4-induced suppressive effects were observed even when IL-4 was administered 2 h post-LPS-stimulation. The IL-4-induced inhibition of IL-8 mRNA expression was dependent on protein synthesis, as the suppressive effects of IL-4 were significantly negated by the addition of cycloheximide. Our findings suggest that IL-4 may be an important endogenous regulator of inflammatory cell recruitment, and adds further support to the potential role of IL-4 as a down-regulator of monocyte immune function.
外周血单核细胞通过产生多种生物活性物质，包括最近分离和克隆的趋化肽白细胞介素-8（IL-8），成为炎症的重要介质。通过细胞因子网络，单核细胞衍生的细胞因子能够诱导非免疫细胞表达IL-8。白细胞介素-4（IL-4）是一种B和T淋巴细胞刺激因子，最近已被证明可抑制单核细胞/巨噬细胞功能，包括抑制单核细胞产生细胞因子的能力。我们描述了IL-4对脂多糖（LPS）、肿瘤坏死因子（TNF）和白细胞介素-1（IL-1）刺激的外周血单核细胞中IL-8基因表达和合成的体外抑制作用。IL-4以剂量依赖的方式抑制刺激的单核细胞产生IL-8，在低至10 pg/ml的IL-4浓度下即可观察到部分抑制作用。即使在LPS刺激后2小时给予IL-4，也能观察到IL-4诱导的抑制作用。IL-4诱导的对IL-8 mRNA表达的抑制作用依赖于蛋白质合成，因为添加放线菌酮可显著消除IL-4的抑制作用。我们的研究结果表明，IL-4可能是炎症细胞募集的重要内源性调节因子，并进一步支持了IL-4作为单核细胞免疫功能下调因子的潜在作用。
