Nielsen O H, Køppen T, Rüdiger N, Horn T, Eriksen J, Kirman I
Department of Medical Gastroenterology C, Herlev Hospital, University of Copenhagen, Denmark.
Dig Dis Sci. 1996 Sep;41(9):1786-93. doi: 10.1007/BF02088746.
The pathogenesis of ulcerative colitis (UC) and Crohn's disease (CD) may be associated with a decreased production of cytokines suppressing macrophage and T-cell functions: interleukins (IL) -4 and IL-10. Serum concentrations of IL-4 and IL-10 were measured using an ELISA technique, and intestinal IL-4 and IL-10 mRNA was detected by a reverse transcriptase polymerase chain reaction (RT-PCR) in 34 patients with inflammatory bowel disease (IBD) (20 with UC and 14 with CD) and compared to 12 control subjects. The superoxide production was measured spectrophotometrically in activated PMNs initially incubated in the presence of IL-4 or IL-10. No differences were found in numbers of cells that might be potential IL-4 or IL-10 producers (T cells, macrophages, B cells, and mast cells) in biopsy specimens using immuno- and histochemistry. IL-4 mRNA was detectable in specimens from 77.8% of the UC patients (P > 0.05) and 0% of the CD patients (P < 0.05), as compared to 81.8 in controls, and was significantly different (P < 0.0001) between UC and CD patients. The IL-10 amplification product was detectable in specimens from 30.0% UC patients (P < 0.003), but not in CD patients (78.6%, P > 0.05) as compared to controls (91.7%). The circulating protein levels of IL-4 were below the detection limit in all groups (detection limit 4 pg/ml), while the median IL-10 concentration was 12.5 pg/ml in UC, 18.1 pg/ml in CD, and 19.5 pg/ml among controls (detection limit 3 pg/ml), which did not differ in any of the three groups (P > 0.05). Finally, the superoxide production was inhibited and delayed by the addition of IL-10 (P < 0.01), whereas IL-4 only delayed this parameter. In conclusion, apart from the well-known suppressive effect on proinflammatory cytokine production, IL-4 delays and IL-10 inhibits superoxide generation. IL-4 mRNA expression is decreased in intestinal tissue from CD patients, while IL-10 mRNA expression is decreased in majority of UC patients, suggesting different immunopathogenesis of the two diseases.
溃疡性结肠炎（UC）和克罗恩病（CD）的发病机制可能与抑制巨噬细胞和T细胞功能的细胞因子——白细胞介素（IL）-4和IL-10分泌减少有关。采用酶联免疫吸附测定（ELISA）技术检测IL-4和IL-10的血清浓度，并通过逆转录聚合酶链反应（RT-PCR）检测34例炎症性肠病（IBD）患者（20例UC患者和14例CD患者）的肠道IL-4和IL-10信使核糖核酸（mRNA），并与12名对照受试者进行比较。在最初于IL-4或IL-10存在的情况下孵育的活化多形核中性粒细胞（PMN）中，用分光光度法测定超氧化物的产生。使用免疫组织化学方法，在活检标本中未发现可能是潜在的IL-4或IL-10产生细胞（T细胞、巨噬细胞、B细胞和肥大细胞）数量的差异。与对照组的81.8%相比，UC患者标本中77.8%可检测到IL-4 mRNA（P>0.05），CD患者标本中0%可检测到（P<0.05），UC和CD患者之间存在显著差异（P<0.0001）。与对照组（91.7%）相比，30.0%的UC患者标本中可检测到IL-10扩增产物（P<0.003），而CD患者标本中未检测到（78.6%，P>0.05）。所有组中IL-4的循环蛋白水平均低于检测限（检测限为4 pg/ml），而UC患者中IL-10的中位数浓度为12.5 pg/ml，CD患者中为18.1 pg/ml，对照组中为19.5 pg/ml（检测限为3 pg/ml）——三组之间无差异（P>0.05）。最后，添加IL-10可抑制并延迟超氧化物的产生（P<0.01），而IL-4仅延迟该参数。总之，除了对促炎细胞因子产生的众所周知的抑制作用外，IL-4延迟、IL-10抑制超氧化物的生成。CD患者肠道组织中IL-4 mRNA表达降低，而大多数UC患者中IL-10 mRNA表达降低，提示这两种疾病的免疫发病机制不同。
