de Waal Malefyt R, Figdor C G, Huijbens R, Mohan-Peterson S, Bennett B, Culpepper J, Dang W, Zurawski G, de Vries J E
Department of Human Immunology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304-1104.
J Immunol. 1993 Dec 1;151(11):6370-81.
Recently, we described the cloning and expression of a human cDNA which is the homologue to P600, a gene transcribed by mouse Th2 clones. Based on its activities on human monocytes and B cells this gene was designated IL-13. In the present study we investigated the effects of IL-13 alone or in combination with IL-4, IFN-gamma, or IL-10 on human monocytes. IL-13 induced significant changes in the phenotype of monocytes. Like IL-4, it enhanced the expression of CD11b, CD11c, CD18, CD29, CD49e (VLA-5), class II MHC, CD13, and CD23, whereas it decreased the expression of CD64, CD32, CD16, and CD14 in a dose-dependent manner. IL-13 induced up-regulation of class II MHC Ag and its down-regulatory effects on CD64, CD32, and CD16 expression were prevented by IL-10. IFN-gamma could also partially prevent the IL-13-induced down-regulation of CD64, but not that of CD32 and CD16. However, IL-13 strongly inhibited spontaneous and IL-10- or IFN-gamma-induced ADCC activity of human monocytes toward anti-D coated Rh+ erythrocytes, indicating that the cytotoxic activity of monocytes was inhibited. Furthermore, IL-13 inhibited production of IL-1 alpha, IL-1 beta, IL-6, IL-8, IL-10, IL-12 p35, IL-12 p40, macrophage inflammatory protein-1 alpha, granulocyte/macrophage-CSF, granulocyte-CSF, IFN-alpha, and TNF alpha by monocytes activated with LPS. In contrast, IL-13 enhanced the production of IL-1 ra by these cells. Similar results on cytokine production were observed or have been obtained with IL-4. Thus IL-13 shares most of its activities on human monocytes with IL-4, but no additive or synergistic effects of IL-4 and IL-13 on human monocytes were observed, suggesting that these cytokines may share common receptor components. Taken together, these results indicate that IL-13 has anti-inflammatory and important immunoregulatory activities.
最近，我们描述了一种人类cDNA的克隆和表达，它是与P600同源的基因，P600是由小鼠Th2克隆转录的基因。基于其对人单核细胞和B细胞的作用，该基因被命名为IL-13。在本研究中，我们研究了IL-13单独或与IL-4、IFN-γ或IL-10联合对人单核细胞的影响。IL-13诱导单核细胞表型发生显著变化。与IL-4一样，它增强了CD11b、CD11c、CD18、CD29、CD49e（VLA-5）、II类MHC、CD13和CD23的表达，而它以剂量依赖的方式降低了CD64、CD32、CD16和CD14的表达。IL-13诱导II类MHC Ag上调，并且IL-10可阻止其对CD64、CD32和CD16表达的下调作用。IFN-γ也可部分阻止IL-13诱导的CD64下调，但不能阻止CD32和CD16的下调。然而，IL-13强烈抑制人单核细胞对抗-D包被的Rh+红细胞的自发以及IL-10或IFN-γ诱导的ADCC活性，表明单核细胞的细胞毒活性受到抑制。此外，IL-13抑制LPS激活的单核细胞产生IL-1α、IL-1β、IL-6、IL-8、IL-10、IL-12 p35、IL-12 p40、巨噬细胞炎性蛋白-1α、粒细胞/巨噬细胞集落刺激因子、粒细胞集落刺激因子、IFN-α和TNFα。相反，IL-13增强了这些细胞产生IL-1ra。用IL-4观察到或已获得关于细胞因子产生的类似结果。因此，IL-13在人单核细胞上具有与IL-4大部分相同的活性，但未观察到IL-4和IL-13对人单核细胞有相加或协同作用，提示这些细胞因子可能共享共同的受体成分。综上所述，这些结果表明IL-13具有抗炎和重要的免疫调节活性。
