梗阻性黄疸内毒素血症与细胞免疫功能的关系

目的研究梗阻性黄疸免疫功能及其与内毒素血症的相关性．方法检测２８例梗阻性黄疸患者及２０例健康对照者血清内毒素，Ｔ淋巴细胞亚群及血清ＳＩＬ２Ｒ的水平．结果梗阻性黄疸患者血清内毒素和ＳＩＬ２Ｒ水平较对照组明显升高（４７０ｎｇ／Ｌ±１１３ｎｇ／Ｌ和７２５ｋＵ／Ｌ±２０１ｋＵ／Ｌｖｓ２８４ｎｇ／Ｌ±１０３ｎｇ／Ｌ和３２４ｋＵ／Ｌ±１１６ｋＵ／Ｌ，Ｐ＜００１），Ｔ淋巴细胞亚群ＣＤ３，ＣＤ４，ＣＤ４／ＣＤ８明显降低（５０４％±３３％和２９９％±３８％ｖｓ６３８％±４４％和３８３％±２８％，Ｐ＜００１；１２２±０３２ｖｓ１４３±０３７，Ｐ＜００５），同时亦发现梗阻性黄疸内毒素血症组较非内毒素血症组ＣＤ３，ＣＤ４水平明显减低，ＳＩＬ２Ｒ水平明显升高（４７４％±５１％和２７６％±５２％和８６７ｋＵ／Ｌ±２３１ｋＵ／Ｌｖｓ５２３％±５２％和３１２％±４３％和６７４ｋＵ／Ｌ±１８９ｋＵ／Ｌ，Ｐ＜００５）．相关分析显示血清内毒素水平与血清ＳＩＬ２Ｒ水平呈显著正相关（ｒ＝０８５１７，Ｐ＜００１）．结论梗阻性黄疸时内毒素血症与免疫功能状态密切相关．     

溃疡性结肠炎患者血清TNFα和IL-8的临床研究

目的研究血清ＴＮＦα和ＩＬ８在溃疡性结肠炎（ＵＣ）发生发展中的作用和意义．方法利用双抗体夹心ＥＬＩＳＡ法测定３３例ＵＣ患者（男１７例，女１６例；年龄２５岁～６７岁；病程２个月～１５ａ；轻型７例，中型２０例，重型６例）及正常对照者４０例，血清ＴＮＦα和ＩＬ８水平．结果活动性ＵＣ患者血清ＴＮＦα（２６２２ｎｇ／Ｌ±２０ｎｇ／Ｌｖｓ１４６２ｎｇ／Ｌ±２５ｎｇ／Ｌ，Ｐ＜００５）和ＩＬ８（１１１８ｎｇ／Ｌ±２６ｎｇ／Ｌｖｓ５７５ｎｇ／Ｌ±４０ｎｇ／Ｌ，Ｐ＜００５）水平明显增高，并与病情的轻重和病变的范围有关（Ｐ＜００５）．结论ＵＣ患者血清ＴＮＦα和ＩＬ８水平增高可能与ＵＣ的发生发展有关，它可作为ＵＣ病情判断的指标．     

血清CA-50含量对消化系肿瘤的诊断价值

目的评价血清ＣＡ＿５０对消化系肿瘤的诊断价值．方法消化系肿瘤患者１７２例，其中肝癌５４例，胃癌４３例，大肠癌５７例，胰腺癌１８例；消化系良性疾病患者８８例，其中肝硬变３６例，胃良性病变（胃炎、胃溃疡）５２例；正常对照者６０例．全部受测对象均抽空腹静脉血，分离血清，－２０℃贮存备测．采用ＲＩＡ法测定血清ＣＡ５０含量．放免药盒由中国医学科学院肿瘤研究所提供，使用国产ＦＪ６３０型γ计数仪．数据均用ｘ±ｓ表示，以正常ｘ＋２ｓ作为上限计算阳性率．结果肝癌、胃癌、胰腺癌和大肠癌血清ＣＡ５０含量分别为２４０ｋＵ／Ｌ±２１８ｋＵ／Ｌ，１２１ｋＵ／Ｌ±１０６ｋＵ／Ｌ，１８２ｋＵ／Ｌ±１０７ｋＵ／Ｌ和１６１ｋＵ／Ｌ±１１３ｋＵ／Ｌ．显著高于正常对照组及消化道良性病变组（分别为５６ｋＵ／Ｌ±４４ｋＵ／Ｌ和５６ｋＵ／Ｌ±２１ｋＵ／Ｌ，Ｐ＜００１）．消化道肿瘤有腹腔及远处转移者，其血清ＣＡ５０含量升高更为明显．结论ＣＡ５０是较好的肿瘤标记物，有助于诊断消化道肿瘤．     

大肠癌患者血清sIL-2R和TNF检测的临床意义

目的研究大肠癌患者血清可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）和肿瘤坏死因子（ＴＮＦ）变化的临床意义．方法采用双抗体夹心ＥＬＩＳＡ法对７６例大肠癌患者手术前后血清ｓＩＬ－２Ｒ和ＴＮＦ水平进行检测，其中根治性手术４８例，姑息性手术２８例，以４０例献血员为正常对照组．结果大肠癌患者血清ｓＩＬ－２Ｒ（Ｕ／Ｌ）和ＴＮＦ（ｐｇ／Ｌ）分别为６０３６±９４３和９６２±９１，明显高于正常对照组的２０８３±７９６和２５１±４７（Ｐ＜００１），两者的增高与大肠癌Ｄｕｋｅ分期及手术方式不同密切相关．结论动态观察血清ｓＩＬ－２Ｒ和ＴＮＦ的变化，可作为大肠癌诊断、评价疗效及监测预后的参考指标．     

结肠癌患者血清可溶性sIL-2R含量的变化

目的探讨结肠癌患者手术前血清可溶性白介素２受体（ｓｏｌｕｂｌｅｉｎｔｅｒｌｕｋｉｎ２ｒｅｃｅｐｔｏｒ，ｓＩＬ２Ｒ）含量改变与疾病的诊断、分期、预后判断等的关系．方法采用ＥＬＩＳＡ法对２７例结肠癌患者（ＤｕｋｅｓＡ，Ｂ期１９例），Ｃ，Ｄ期８例）及４２例对照组（正常３２例及肠易激综合征１０例）分别测定血清ｓＩＬ２Ｒ含量．同时使用间接荧光染色法对各组进行血ＣＤ３，ＣＤ４，ＣＤ８及ＣＤ４／ＣＤ８的测定．结果结肠癌患者ＤｕｋｅｓＡ，Ｂ期组血清ｓＩＬ２Ｒ含量（８３５ｐｍｏｌ／Ｌ±２１８ｐｍｏｌ／Ｌ）与对照组（６９２ｐｍｏｌ／Ｌ±２７９ｐｍｏｌ／Ｌ及７６２ｐｍｏｌ／Ｌ±２４６ｐｍｏｌ／Ｌ）无明显差异，而有淋巴结转移的ＤｕｋｅｓＣ，Ｄ期患者（３２１６ｐｍｏｌ／Ｌ±２３４４ｐｍｏｌ／Ｌ）则明显高于ＤｕｋｅｓＡ，Ｂ期患者，且ＣＤ４／ＣＤ８值明显下降（１０６±０４９比１５８±０３６）；另外，血清ｓＩＬ２Ｒ含量还与肿瘤细胞分化程度密切关联．结论结肠癌术前血清ｓＩＬ２Ｒ含量与疾病分期及预后有关．     

乙型肝炎及原发性肝癌患者sIL-2R的变化

目的探讨ｓＩＬ２Ｒ水平与乙型肝炎病情的关系及其在原发性肝癌早期诊断中的价值．方法以ＥＬＩＳＡ法动态检测１１３例乙型肝炎及６例原发性肝癌患者ｓＩＬ２Ｒ水平，另选３１例健康体检者作对照组．结果以ｑ检验、ｔ检验进行统计学处理（微机处理，ＰＯＭＳ２００版）．结果各型乙型肝炎ｓＩＬ２Ｒ水平均显著高于正常对照（ＮＣ）组（Ｐ＜００１），其顺序依次为：ＨＣＣ＞ＣＳＨ＞ＣＨ（ＩＩ）＞ＬＣ＞ＣＨ（ＩＩ）＞ＡＨ＞ＣＨ（Ｉ）＞ＮＣ．ＨＣＣ组ｓＩＬ２Ｒ均值达正常值的２倍以上，且与ＣＨ（Ｉ），ＣＨ（Ｉ），ＡＨ间存在显著性差异（Ｐ＜００１，＜００５及＜００５）；ＣＨ（ＩＩ）组显著高于ＣＨ（Ｉ）组（Ｐ＜００１）．ＨＢｅＡｇ阳性组及ＨＢＶＤＮＡ阳性组ｓＩＬ２Ｒ水平显著高于阴性组．结论ｓＩＬ２Ｒ是监测乙型肝炎病情、ＨＢＶ复制及诊断早期原发性肝癌的一项敏感标志．     

慢性胃炎血清sIL─2R及RBC免疫功能的研究

目的研究慢性胃炎患者血清ｓＩＬ＿２Ｒ及ＲＢＣ免疫功能的变化。方法内镜及病理检查确诊的慢性胃炎５１例和４０例正常对照组作血清ｓＩＬ＿２Ｒ（双抗体夹心ＥＬＩＳＡ法）及ＲＢＣＣ３ｂ受体花环率、ＲＢＣ免疫复合物花环率（酵母菌花环试验）测定。结果慢性胃炎患者血清ｓＩＬ＿２Ｒ水平（２７５０±２３１１ＫＵ／Ｌ）与正常对照组（１９０６±７９３ＫＵ／Ｌ）相比增高，ＲＢＣ免疫功能降低；上述改变在慢性萎缩性胃炎及合并Ｈｐ感染者更明显（Ｐ＜００１）。血清ｓＩＬ＿２Ｒ与ＲＢＣＣ３ｂＲＲ呈负相关（ｒ＝－０５７，Ｐ＜００１）；与ＲＢＣＩＣＲ呈正相关（ｒ＝０７２，Ｐ＜００１）。结论慢性胃炎患者有免疫功能紊乱，血清ｓＩＬ＿２Ｒ及ＲＢＣ免疫功能低下，可能与慢性胃炎的发生发展有关     

冬虫夏草多糖治疗慢性丙型肝炎患者的临床研究

目的研究冬虫夏草多糖（ＣＰ）治疗慢性丙型肝炎的疗效．方法慢性丙型肝炎患者２１例，口服ＣＰ１５ｍＬ，３次／ｄ，连服３ｍｏ，治疗前后检测肝功能、血清肝纤维化标志物外周血Ｔ细胞亚群及ＮＫ活性的变化．结果慢性丙型肝炎患者经ＣＰ治疗后，血清ＡＬＴ（Ｕ／Ｌ，６１±３５ｖｓ３５±１５）及ｒＧＴ（Ｕ／Ｌ，１６９±８５ｖｓ１１８±５２）较治疗前显著降低（Ｐ＜００５）．血清ＨＡ（μｇ／Ｌ，２９３±１０９ｖｓ２１４±９６）、ＰⅢＰ（μｇ／Ｌ，１４３±４８ｖｓ１１４±４２）及ＣⅣ（μｇ／Ｌ，２４５±９８ｖｓ１８８±８７）均较治疗前显著下降（Ｐ＜００１，＜００５及＜００５）；ＣＤ４（３６４％±６６％ｖｓ４１０％±５６％）、ＣＤ４／ＣＤ８（１１４±０４０ｖｓ１４３±０２２）、ＮＫ（１６７％±４６％ｖｓ１９７％±４２％）均较治疗前显著增加（Ｐ＜００１），而ＣＤ８（３２６％±４７％ｖｓ２８９％±３７％）则明显降低（Ｐ＜００５）；血清胆红素略减、清蛋白略增但差异均无显著性．结论冬虫夏草多糖可以增强慢性丙型肝炎患者细胞免疫功能，改善肝功能，并具有一定的抗纤维化作用     

肺结核患者血清可溶性白细胞介素－2受体测定的研究

采用酶联免疫吸附法检测了４０例初治菌阳肺结核患者和３０名健康人的血清可溶性白细胞介素－２受体（ｓＩＬ－２Ｒ）水平。其中对１８例患者于抗结核治疗１、２、３个月再次取血标本测定，并分析了ｓＩＬ－２Ｒ与病情变化的相关性。结果显示：肺结核患者的ｓＩＬ－２Ｒ水平治疗前为１２６６±９６２ｋＵ／Ｌ，治疗后３个月为５０７±１０８ｋＵ／Ｌ，与对照组（２３２±７２ｋＵ／Ｌ）相比均有显著性增高（Ｐ＜０．００１）。１８例患者ｓＩＬ－２Ｒ水平治疗前为１２５０±８９４ｋＵ／Ｌ，显著高于治疗后３个月的５０７±１０８ｋＵ／Ｌ（Ｐ＜０．００１）。治疗前患者血清ｓＩＬ－２Ｒ水平与病程、病变、空洞及治疗后与临床症状、病变、痰菌等有平行关系。这些结果提示ｓＩＬ－２Ｒ可作为肺结核诊断、病情监测及预后估计的一项参考指标。     

原发性肝癌血清性激素及组织性激素受体的研究

目的研究人体性激素水平变化与原发性肝细胞癌的关系．方法应用放免法测定肝癌组（２０例），肝硬变组（１６例）及正常对照组（２０例）血清雌二醇（Ｅ２）及睾酮（ＴＴＴ）含量，并用放免组化法（ＰＡＰ法）检测肝癌组织及肝硬变组织的雌二醇受体（ＥＲ）及睾酮受体（ＡＲ）含量．结果肝癌组血清Ｅ２含量（４４５５±９３１ｎｇ／Ｌ）明显高于正常对照组（７６６ｎｇ／Ｌ±１７０ｎｇ／Ｌ）而低于肝硬变组（６４９６ｎｇ／Ｌ±１７６ｎｇ／Ｌ）（Ｐ＜００１）；前者ＴＴＴ含量（２５３３００ｎｇ／Ｌ±５６５６０ｎｇ／Ｌ）明显低于后二者（４５８５８０ｎｇ／Ｌ±３４９６０ｎｇ／Ｌ）（Ｐ＜００１）．肝癌组织ＥＲ（８０％）较肝硬变时（４４％）明显增加（Ｐ＜００２５），且与血清Ｅ２含量有明显负相关关系（ｒ＝－０８４７３，Ｐ＜０００１）．ＡＲ阳性百分率在两者无明显差别（ｒ＝－０３１３５，Ｐ＞００５）．结论血清ＴＴＴ含量改变及肝组织ＡＲ浓度改变与肝癌无明显关系，而血清Ｅ２含量改变及肝组织ＥＲ浓度改变与肝癌的发生、发展有密切关系．提示原发性肝细胞癌是一雌激素依赖性肿瘤．     

Increased in vitro release of soluble interleukin 2 receptor by colonic lamina propria mononuclear cells in inflammatory bowel disease.

Increased concentrations of the soluble form of the interleukin 2 receptor have been observed in the sera of Crohn's disease and ulcerative colitis patients. In this study we have observed the spontaneous release of soluble interleukin 2 receptor by unstimulated, isolated normal and inflammatory bowel disease colonic lamina propria mononuclear cells. Lamina propria mononuclear cells from Crohn's disease patients (median = 204 U/ml (interquartile range 126-396, n 17) secreted significantly (p less than 0.01) more soluble interleukin 2 receptor than normal controls (median = 124.5 U/ml (108-131), n 12). No statistically significant differences were seen between ulcerative colitis (median = 135 U/ml (92-196), n 20) and normal controls. Moreover, significantly (p less than 0.01) increased amounts of soluble interleukin 2 receptor were secreted by colonic diverticulitis lamina propria mononuclear cells (median = 259 U/ml (149-282), n 15) which were used as disease specificity controls. Time course experiments showed that the majority of soluble interleukin 2 receptor was released by isolated lamina propria mononuclear cells in the first six days of culture. Upon stimulation with pokeweed mitogen, Crohn's disease (median = 2258 U/ml (1435-3584), n 14), normal control (median = 2622 U/ml (2030-3180), n 14) and diverticulitis lamina propria mononuclear cells (median = 2745 U/ml (1733-3192), n 10) reached similar maximal soluble interleukin 2 receptor secretion levels, while ulcerative colitis lamina propria mononuclear cells secreted significantly (p less than 0.005) less soluble interleukin 2 receptor (median = 912 U/ml (494-1259), n 17). These results suggest that enhanced shedding/secretion of soluble interleukin 2 receptor by intestinal lymphocytes may account in part for increased serum soluble interleukin 2 receptor concentrations during chronic intestinal inflammatory reactions.     

Selective resistance of mucosal T-cell activation to immunosuppression in Crohn''s disease

BACKGROUND & AIMS: The inappropriately high state of T-cell activation found in Crohn's disease could be due to failure to respond to inhibitory signals. We tested the hypothesis that Crohn's disease mucosal T-cells are resistant to the immunosuppressive action of interleukin4. PATIENTS: Patients with Crohn's disease, ulcerative colitis, and other malignant and non-malignant conditions undergoing bowel resection. METHODS: The effect of interleukin-4 on lamina propria mononuclear cells from Crohn's disease, ulcerative colitis and control mucosa was assessed on various T-cell functions: interleukin-2-induced cytotoxicity, soluble interleukin-2 receptor and interleukin-2 production, and expression of mRNA for interleukin-2R and interferon-gamma. RESULTS: Cytotoxicity of control and ulcerative colitis cells was markedly decreased by interleukin-4, whereas Crohn's disease cells failed to be inhibited. Addition of interleukin-4 to interleukin-2-stimulated cultures decreased soluble interleukin-2R production significantly less in Crohn's disease and ulcerative colitis than control cells. In the same cultures, residual levels of interleukin-2 were significantly increased in control and ulcerative colitis, but not Crohn's disease cultures. Finally, Crohn's disease cells were significantly more resistant to interleukin-4-mediated inhibition of spontaneous and interleukin-2-induced expression of interleukin-2Ralpha and interferon-gamma mRNA compared to control cells. CONCLUSIONS: The effector function, receptor expression and cytokine production of Crohn's disease mucosal T-cells are resistant to interleukin4-mediated inhibition. Failure to respond to down-regulatory signals may contribute to persistent T-cell activation and chronicity of inflammation in Crohn's disease.     

Soluble interleukin 2 and CD8 and CD4 receptors in inflammatory bowel disease.

Serum levels of soluble interleukin 2 receptor (sIL-2R) have been proposed as a clinical marker of inflammatory bowel disease. The source of sIL-2R in patients with Crohn's disease and ulcerative colitis is unknown, and other soluble receptors have not been investigated. In the present study, sIL-2R and soluble CD8 and CD4 levels were measured in plasma and culture supernatants of peripheral blood and intestinal mucosal mononuclear cells from patients with inflammatory bowel disease, surgical controls, and healthy subjects. Level of plasma sIL-2R was significantly higher in patients with Crohn's disease and ulcerative colitis than in healthy volunteers. Intestinal cells always produced more sIL-2R than peripheral cells. Spontaneous sIL-2R production by mucosal cells was significantly elevated in Crohn's disease but not in ulcerative colitis supernatants compared with levels of surgical controls. Soluble CD8 and CD4 were poor indicators of systemic or mucosal immunity. A positive correlation was found between plasma sIL-2R and spontaneous production by intestinal cells of patients with Crohn's disease and surgical control patients, whereas ulcerative colitis plasma sIL-2R correlated with spontaneous production by peripheral cells. The association of plasma or spontaneous sIL-2R levels with the degree of intestinal inflammation was weak, and there was a wide overlap with control values. Therefore, caution should be used before considering sIL-2R an accurate marker of inflammatory bowel disease activity.     

Deficient interleukin 2 dependent proliferation pathway in T lymphocytes from active and inactive ulcerative colitis patients.

There is increasing evidence that ulcerative colitis is associated with an abnormality of the immune system. Although the aetiology remains unknown, it has been suggested that the immune system of these patients is implicated in the pathogenesis of their disease. T cell function was investigated in ulcerative colitis patients and defective phytohaemagglutinin induced T cell mitogenesis was found. The DNA synthesis induced by stimulation with phorbol esters plus ionophore (ionomycin), however, was normal. These changes cannot be ascribed to either decreased interleukin 2 synthesis or to a defective interleukin 2 receptor expression after cellular activation. Moreover, this defective proliferative response of the T lymphocytes was observed even in the presence of saturated concentrations of exogenous interleukin 2. These results emphasise that the interleukin 2 dependent proliferation pathway is deficient in T lymphocytes from ulcerative colitis patients.     

Soluble interleukin-6 receptors in inflammatory bowel disease: relation to circulating interleukin-6.

The in vivo appearance of soluble interleukin (IL)-6 receptor (sIL-6R) in serum from patients with inflammatory bowel disease was examined using an enzyme linked immunosorbent assay (ELISA). The serum sIL-6R concentrations in patients with active disease (ulcerative colitis, 148.4 (5.1); Crohn's disease, 142.3 (9.3) ng/ml; mean (SEM)) were significantly raised compared with those in patients with inactive disease (ulcerative colitis, 116.2 (7.2); Crohn's disease, 114.3 (7.1) ng/ml), some other type of colitis (104.8 (11.6) ng/ml), or in normal subjects (107.3 (2.4) ng/ml). These differences were also seen in paired samples examined during both active and inactive phases. Additionally, serum sIL-6R and IL-6 concentrations correlated significantly with C-reactive protein levels in both ulcerative colitis and Crohn's disease patients (r = 0.23 and 0.56, respectively; p < 0.05 for both). Furthermore, gel filtration analysis of serum from these patients showed two major peaks of immunoreactive IL-6-one peak corresponding to free IL-6 and another peak to sIL-6R-bound IL-6-this was further confirmed by a luminescence sandwich ELISA. These results, together with its in vitro effects, indicate that natural sIL-6R may function as a powerful enhancer of the IL-6-dependent immune processes observed in inflammatory bowel disease.     

In vitro production of TNF-alpha,IL-6 and sIL-2R in Chinese patients with ulcerative colitis

AIM:To determine the tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and soluble interleukin 2 receptor (sIL-2r) from peripheral blood mononuclear cells (PBMC) in 25 Chinese patients with ulcerative colitis and 20 healthy controls.METHODS:PBMC were isolated by density gradient centrifugation of heparinized blood and cultures for 24 or 48 hours by stimulation with LPS or PHA. TNF-alphaand sIL-2r were measured by ELISA method and IL-6 measured by biossay.RESULTS:TNF-alphaproduction stimulated by LPS and sIL-2r production by PHA in ulcerative colitis were significantly lower than in healthy controls (TNF-alpha509(46-7244)ng/L vs 1995(117-18 950)ng/L, P < 0.05; sIL-2r 320U/mlplus minus 165U/ml vs 451U/mlplus minus 247U/ml, P < 0.05).Spontaneous TNF-alphaand sIL-2r production were not significantly different between ulcerative colitis and controls (TNF-alpha304(46-7044)ng/L vs 215(46-4009)ng/L,P > 0.05; sIL-2r 264U/mlplus minus 115U/ml vs 236U/mlplus minus139U/ml, P>0.05). IL-6 production by spontaneous release from PBMC in ulcerative colitis group was 109U/mlplus minus 94U/ml vs 44U/mlplus minus 39U/ml for those in healthy controls, P < 0.01. IL-6 stimulated by LPS in ulcerative colitis group was (261U/ml plus minus 80U/ml) higher than in healthy controls (102U/mlplus minus 54U/ml, P < 0.01). No correlation of TNF-alpha, IL-6, sIL-2r production was found to disease activity, disease location and medication.CONCLUSION:Cytokine production from PBMC was also disturbed in Chinese patients with ulcerative colitis.     

Oral 4-aminosalicylic acid versus 5-aminosalicylic acid slow release tablets. Double blind, controlled pilot study in the maintenance treatment of Crohn's ileocolitis.

4-Aminosalicylic acid (4-ASA) has been suggested as an effective treatment for both active and quiescent ulcerative colitis. 5-Aminosalicylic acid (5-ASA) is well accepted for the maintenance treatment of inactive ulcerative colitis. Moreover, recent studies suggest that 5-ASA may also be effective in maintaining remission in Crohn's colitis. As treatment with 4-ASA may result in less side effects, the efficacy of a one year's maintenance treatment with oral 4-ASA (1.5 g/d, slow release tablets, n = 19) and oral 5-ASA (1.5 g/d, slow release tablets, n = 21) was compared in a double blind, randomised trial in patients with quiescent Crohn's ileocolitis. Patients with ileocolonic or colonic involvement were enrolled if in stable remission for more than two months but less than one year. Baseline demography and clinical severity were similar in both groups. Total colonoscopy and ileoscopy were performed at enrollment and at the end of the study. After one year seven of 19 patients receiving 4-ASA (36%) and 8 of 21 receiving 5-ASA (38%) had developed a clinical relapse, as defined by a rise in the Crohn's disease activity index (CDAI) of more than 100 points to values higher than 150. The relapse rates between the 4-ASA and the 5-ASA groups were not statistically different although no comparison with the spontaneous relapse rate in a placebo group could be made. Clinical relapse was accompanied by a statistically significant rise in serum concentrations of soluble interleukin 2 receptor and by an increased percentage of activated peripheral blood T cells. There were no statistical differences between the 4-ASA and the 5-ASA groups regarding the height of rise in CDAI or of soluble interleukin 2 receptor concentrations during relapse, thus showing a similar severity relapsed disease activity. In conclusion, 4-ASA maybe as effective as 5-ASA in the maintenance treatment of quiescent Crohn's disease and there were no differences in the severity of relapse between both treatment groups.     

The interleukin 1 receptor antagonist gene allele 2 as a predictor of pouchitis following colectomy and IPAA in ulcerative colitis

BACKGROUND & AIMS: The interleukin 1 receptor antagonist gene allele 2 has been suggested as a determinant of both disease susceptibility and extent in ulcerative colitis. The aim of this study was to assess the allele as a predictor of both the indication for colectomy and the occurrence of pouchitis after ileal pouch-anal anastomosis formation. METHODS: Genotyping for the +2018 single nucleotide polymorphism in the interleukin 1 receptor antagonist gene was performed in 109 patients who had undergone colectomy, including 82 patients who had been followed prospectively after ileal pouch-anal anastomosis formation. RESULTS: Patients with pouchitis had a higher allele 2 carriage rate compared with those without pouchitis (72% vs. 45%) and Kaplan-Meier survival analysis showed that allele 2 carriers had a significantly increased incidence of pouchitis compared with noncarriers (log-rank test, 6.5). After adjustment for confounding covariates in a Cox proportional hazards model, the relative hazard was 3.1 (95% confidence interval [CI], 1.2-7.8; P = 0.02). Although there was a higher allele 2 carriage rate in patients with chronic refractory compared with acute severe ulcerative colitis (63% vs. 48%), this difference was not significant (odds ratio, 1.9; 95% CI, 0.9-4.1; P = 0.1). CONCLUSIONS: The interleukin 1 receptor antagonist gene allele 2 predicts pouchitis after ileal pouch-anal anastomosis in ulcerative colitis.     

Alterations in serum immunoglobulin G subclasses in patients with ulcerative colitis and Crohn's disease

We have examined the concentration of immunoglobulin G (IgG) subclass antibodies in the sera of 27 patients with ulcerative colitis and 21 patients with Crohn's disease as well as in 11 normal controls and 11 patients with systemic lupus erythematosus. In comparison with a control mean serum IgG1 concentration of 5173 micrograms/ml, patients with ulcerative colitis exhibited a significantly increased mean serum concentration of 7924 micrograms/ml (p less than 0.05), whereas patients with Crohn's disease had a near normal mean serum IgG1 level of 5898 micrograms/ml. In contrast, control sera had a mean IgG2 level of 2477 micrograms/ml and ulcerative colitis sera had a similar IgG2 level of 2269 micrograms/ml, whereas Crohn's disease sera had a significantly increased mean IgG2 level of 5111 micrograms/ml (p less than 0.05). Patients with systemic lupus erythematosus, like those with ulcerative colitis, had a markedly elevated serum IgG1 level of 15,594 micrograms/ml (p less than 0.001) without a significantly increased IgG2 serum level (3271 micrograms/ml). Neither ulcerative colitis nor Crohn's disease sera exhibited altered levels of IgG3 or IgG4. These data show that alterations in IgG subclass concentrations occur in the sera of patients with active, untreated inflammatory bowel disease, similar to the previously noted changes in the IgG subclasses secreted by lymphocytes from involved inflammatory bowel disease intestinal specimens.     

Association of the interleukin 1 receptor antagonist gene with ulcerative colitis in Northern European Caucasians

BACKGROUND AND AIMS: An association between the allele 2 of the interleukin 1 receptor antagonist gene variable number tandem repeats polymorphism in intron 2 and ulcerative colitis was first reported in 1994. Subsequent studies in Caucasian Northern European patients have not confirmed this, although trends towards an association were observed. The lack of statistical significance could reflect inadequate power. In this study the association was reassessed in a large independent set of well characterised Caucasian patients and a meta-analysis of reported patient series was performed. PATIENTS AND METHODS: A total of 320 patients with endoscopically and histologically confirmed ulcerative colitis (124 pancolitis, 196 left sided and distal disease) and 827 ethnically matched controls were genotyped at polymorphic sites in the interleukin 1 receptor antagonist gene. Carriage rates were compared using chi(2) statistics. A meta-analysis of this and seven previous studies in North European Caucasian patients was performed using the Mantel-Haenszel chi(2) test. RESULTS: Patients had a significantly increased carriage rate of allele 2 compared with controls (52% v 45%; odds ratio 1.3 (95% confidence interval (CI) 1.01-1.7); p=0.04). The allele 2 carriage rate was highest in extensive colitis (carriage rate 56%; odds ratio 1.5 (95% CI 1.1-2.3) p=0.02) and in individuals who had undergone colectomy (carriage rate 55%; odds ratio 1.5 (95% CI 0.95-2.4); p=0.08). Meta-analysis of all eight studies showed a significant association between carriage of allele 2 and ulcerative colitis (odds ratio 1.23 (95% CI 1.04-1.45); p=0.01). CONCLUSIONS: The association of the interleukin 1 receptor antagonist gene polymorphism with ulcerative colitis is confirmed. The association is minor and confers only a small risk to an individual but will contribute a high attributable risk in a population due to the high allelic frequency. Accurate phenotypic characterisation defines more homogeneous subsets of patients, such as those with extensive disease, in whom the association is greater.