Autschbach F, Braunstein J, Helmke B, Zuna I, Schürmann G, Niemir Z I, Wallich R, Otto H F, Meuer S C
Institute of Pathology, German Cancer Research Center, Heidelberg.
Am J Pathol. 1998 Jul;153(1):121-30. doi: 10.1016/S0002-9440(10)65552-6.
A dysregulated secretion of contra-inflammatory cytokines such as interleukin-10 (IL-10) could play a role in the pathogenesis of inflammatory bowel disease (IBD). We have investigated the expression of IL-10 in gut tissues from patients with Crohn's disease (CD), ulcerative colitis (UC) and controls by mRNA in situ hybridization and immunohistochemistry. Intestinal epithelial cells were found to express IL-10 mRNA and IL-10 protein in all of the tissues investigated without any major differences in the expression patterns. However, compared with noninflamed gut, significantly increased numbers of mononuclear cells (MNCs) producing IL-10 were present in inflamed gut, both in CD and UC. This cytokine was expressed most prominently by inflammatory infiltrates enriched in macrophages, although T cells seem to contribute to its production as well. Elevated IL-10 expression in IBD was mainly detected in the submucosa, whereas IL-10 production by lamina propria cells remained comparably low. In contrast, the expression of IL-1beta mRNA was preferentially increased in the lamina propria. Our data argue against a general deficiency in IL-10 production in IBD. The results suggest rather that the local production of IL-10 by mucosal MNCs in IBD is insufficient to down-regulate pro-inflammatory cytokines such as IL-1beta in the lamina propria compartment.
抗炎细胞因子如白细胞介素-10(IL-10)分泌失调可能在炎症性肠病(IBD)的发病机制中起作用。我们通过mRNA原位杂交和免疫组织化学研究了克罗恩病(CD)、溃疡性结肠炎(UC)患者及对照者肠道组织中IL-10的表达。在所有研究的组织中,均发现肠上皮细胞表达IL-10 mRNA和IL-10蛋白,且表达模式无明显差异。然而,与非炎症肠道相比,在CD和UC的炎症肠道中,产生IL-10的单核细胞(MNCs)数量显著增加。这种细胞因子在富含巨噬细胞的炎症浸润中表达最为突出,不过T细胞似乎也参与了其产生。IBD中IL-10表达升高主要在黏膜下层检测到,而固有层细胞产生的IL-10仍然相对较低。相反,IL-1β mRNA的表达在固有层中优先增加。我们的数据反驳了IBD中IL-10产生普遍不足的观点。结果表明,IBD中黏膜MNCs局部产生的IL-10不足以下调固有层隔室中诸如IL-1β等促炎细胞因子。