Significance of interleukin-6 in patients with inflammatory bowel disease

The significance of interleukin-6 (IL-6) in patients with inflammatory bowel disease (IBD) was studied by measuring the IL-6 level in serum and colonic tissue by means of an enzyme-linked immunosorbent assay (ELISA), and by examining its localization using an immunohistochemical method. The serum IL-6 level reflected the degree of disease activity, and the extent of affected area, and was also correlated with the serum C-reactive protein (CRP) level. In the colonic mucosa of active IBD, the tissue IL-6 level was markedly elevated, and immunoreactive products of anti-IL-6 antibody were present in infiltrative mononuclear cells in the lamina propria. This indicates that IL-6 production in these cells is enhanced at the site of affected intestine. These results, together with its biological activity and the type of cell producing it, suggest that IL-6 is an available marker to assess disease conditions of IBD and that it might be also involved in the pathophysiology of IBD.     

Colonic mucosal interleukin-6 in inflammatory bowel disease.

Interleukin-6, a cytokine produced by various cell types, has a major role in inflammatory and immunological reactions. To define its potential role in inflammatory bowel disease, its concentrations in endoscopic biopsy samples from patients with ulcerative colitis and Crohn's disease were measured. The involved colonic mucosa from active disease was found to contain significantly larger amounts of interleukin-6 than that from inactive disease or normal controls. Colonic mucosal interleukin-6 levels correlated well with the grade of macroscopic inflammation, especially in patients with ulcerative colitis. The levels of interleukin-6 decreased in parallel with clinical improvement following the start of therapy in patients with both forms of inflammatory bowel disease. Mucosal interleukin-6 is thus concluded to accurately reflect the degree of colonic inflammation and may be importantly associated with inflammatory and immunological phenomena seen in inflammatory bowel disease.     

High-sensitivity C-reactive protein in paediatric inflammatory bowel disease

AIM:To study whether high-sensitivity C-reactive protein(hs-CRP) measurement can aid the assessment of disease activity and glucocorticoid treatment in paediatric inflammatory bowel disease(IBD).METHODS:CRP levels were measured in 39 children with IBD undergoing colonoscopy [median age 12.8 years,Crohn's disease(CD) n=20],in 22 other children with IBD followed for acute response to glucocorticoids,and in 33 paediatric non-IBD patients.When standard CRP level was below detection limit(<5mg/L),hs-CRP was anal...     

Agalactosyl IgG in inflammatory bowel disease: correlation with C-reactive protein.

The proportion of oligosaccharide chains on the Fc fragment of IgG which terminate with N-acetylglucosamine (GlcNAc) rather than galactose is increased in rheumatoid arthritis and tuberculosis, and in sera from patients with Crohn's disease, probably because of decreased activity of a galactosyltransferase in B lymphocytes. We have assayed the prevalence of agalactosyl oligosaccharides on IgG in sera from 67 patients with inflammatory bowel disease (32 ulcerative colitis and 35 Crohn's disease). The prevalence of agalactosyl IgG significantly increases in the majority of Crohn's patients (19/35 patients), and correlates with the level of C-reactive protein (r = 0.79), and inversely with the concentration of serum albumin. Sera from ulcerative colitis patients show less frequent (nine of 32) and less marked rises in agalactosyl IgG, and sera with high C-reactive protein values can contain normal levels. Thus in ulcerative colitis no correlation was seen between the two assays. The diseases in which the percentage of agalactosyl IgG is raised (rheumatoid arthritis, tuberculosis, Crohn's disease and some ulcerative colitis) are characterised by simultaneous T cell mediated granulomatous tissue damage, and acute phase responses. Levels are normal in less tissue damaging granulomatous conditions, including sarcoidosis, and leprosy (except during episodes of erythema nodosum leprosum). We suggest therefore that a raised percentage of agalactosyl IgG is a correlate of a particular type of T cell mediated pathology which may be relevant to the pathogenesis of inflammatory bowel disease.     

男性冠心病患者血浆睾酮与超敏C反应蛋白、白介素-6及同型半胱氨酸的关系

目的观察男性冠心病患者血浆睾酮水平与血浆中超敏C反应蛋白(hs-CRP)、白介素-6(IL-6)、同型半胱氨酸(Hcy)水平的关系。方法将95例患者分为冠心病组(50例)与对照组(45例),分别检测两组睾酮、hs-CRP、IL-6、Hcy、总胆固醇(TC)、甘油三酯(TG)水平,并收集两组病例年龄、吸烟史、高血压史、体质指数等基本临床信息。结果冠心病组与对照组在年龄、高血压史、吸烟史、体质指数、血脂水平比较差异均无统计学意义(P0.05)。冠心病组与对照组相比,血浆睾酮显著低于对照组,hs-CRP、IL-6、Hcy显著上升(P0.05)。Pearson直线相关分析表明,冠心病组的血浆睾酮水平与hs-CRP(r=-0.760,P0.05)、IL-6(r=-0.625,P0.05)、Hcy(r=-0.529,P0.05)水平呈显著负相关。结论冠心病患者血浆睾酮水平降低,但Hcy及炎性反应水平升高;睾酮的水平与炎性反应水平和Hcy水平呈负相关。     

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.     

白细胞介素23与炎症性肠病

炎症性肠病(IBD)是一类病因不明的胃肠道慢性非特异性炎症,包括克罗恩病(CD)和溃疡性结肠炎(UC).促炎因子和抗炎因子的失衡被视为一个重要的病因[1].白细胞介素23(IL-23)属于前炎性因子,在IBD的发生、发展中起重要作用.此文就近年来IL-23在IBD发生、发展和治疗中的作用作一综述.     

绝经后女性冠心病患者雌激素、C反应蛋白与白介素6水平变化及其关系

目的探讨绝经后女性冠心病患者体内雌激素、C反应蛋白与白介素6水平的变化以及雌激素与C反应蛋白、白介素6的关系。方法对31例符合要求的绝经后女性冠心病患者与44例非冠心病患者股动脉采血检测雌二醇、C反应蛋白与白介素6的浓度。结果冠心病组的雌激素水平明显低于非冠心病组(18±7)vs(24±10)ng/L,P0.05,而C反应蛋白与白介素6水平则明显高于非冠心病组(6.9±5.9)vs(1.9±1.3)mg/L;(59±11)vs(46±13)ng/L,P0.01。雌二醇与C反应蛋白、白介素6没有明显的相关性(r=-0.106,-0.203,P0.05)。结论雌二醇、C反应蛋白和白介素6在绝经后女性冠心病的发病中起着重要的作用。雌激素影响女性冠心病的发病与C反应蛋白以及白介素6没有明显的相关性。     

Significant differences in the interleukin-1beta and interleukin-1 receptor antagonist gene polymorphisms in a Hungarian population with inflammatory bowel disease

BACKGROUND: There is growing evidence of the importance of genetic predisposition and the activation of the mucosal immune system in the pathogenesis of inflammatory bowel disease. Thus, genes involved in the regulation of inflammation are receiving increased attention. We have studied whether Crohn's disease (CD) or ulcerative colitis (UC) is associated with certain allelic combinations of IL1B/IL1RA gene polymorphisms in a different European population than the ones studied so far. METHODS: Ninety-six patients with UC, 97 with CD, and 132 healthy individuals (HC) were typed for the polymorphic regions in exon 5 of the IL1B gene and in intron 2 of the IL1RA gene, using polymerase chain reaction-based methods. RESULTS: In CD homozygotes for allele 1 in IL1B gene polymorphism were more often present (72% versus 28%; P = 0.01) in the subgroup of patients carrying at least one copy of allele 2 in IL1RA gene polymorphism. This association was not found in HC (HC versus CD; P = 0.03) or UC. However, in UC patients with pancolitis a similar trend was observed (75% versus 25%). Several genotype combinations characterized by the presence of allele 2 of the IL1RA gene polymorphism were more common in CD (P = 0.001) and UC (P = 0.049) than in HC. CONCLUSIONS: Our data support the concept that CD and severe UC have a genetic disequilibrium in the distribution of IL1B and IL1RA gene polymorphisms. These findings together with functional studies will contribute to the understanding of the pathogenesis of the chronicity of inflammation in these diseases.     

Increased concentrations of interleukin 1 beta, interleukin-2, and soluble interleukin-2 receptors in endoscopical mucosal biopsy specimens with active inflammatory bowel disease.

Concentrations of interleukin-1 beta (IL-1 beta), interleukin-2 (IL-2), and soluble IL-2 receptors (sIL-2R) were determined by enzyme linked immunosorbent assays (ELISA) in supernatants of sonicated endoscopical mucosal biopsy specimens from 31 patients with inflammatory bowel disease and 19 controls. IL-1 beta was detected in 53% of the patient supernatants (p = 0.0001), IL-2 in 35% (p = 0.0031), compared with none of the controls. Soluble IL-2R was present in 55% and 26% of the specimens, respectively (p = 0.07). The concentrations of IL-1 beta (p = 0.00015), IL-2 (p = 0.0019), and sIL-2R (p = 0.0073) were highest in the most inflamed biopsy specimens, compared with less inflamed specimens and controls. There were no significant differences in IL-1 beta, IL-2, and sIL-2R concentrations between ulcerative colitis (16) and Crohn's disease patients (15). The results suggest that enhanced cellular immunity operates in vivo at the mucosal level in active inflammatory bowel disease.     

IL-17基因多态性与中国汉族人群炎症性肠病的关系

目的:研究IL-17A和IL-17F的5个多态性位点与中国汉族人炎症性肠病之间的关系.方法:采用病例-对照研究方法,收集确诊的溃疡性结肠炎(ulcerative colitis,UC)和克罗恩病(Crohn’s disease,CD)患者共350例(UC270例;CD80例),健康对照组268例,收集外周血标本2mL,提取DNA,运用LDR(ligasedetection reaction allelic)技术进行多态性检测.采用SPSS17.0软件进行数据分析.结果:CD患者中IL-17F(rs763780,7488T/C)突变等位基因C的频率明显高于对照组(13.8%vs8.4%,P=0.044,OR=1.74,95%CI1.01-2.99).在亚型分析中,rs763780基因多态性与CD病变范围有关,突变等位基因C在CD回结肠型患者中的频率明显高于对照组(P=0.02).IL-17A(rs2275913,G-197A)与UC患者疾病的严重程度有弱相关性,含有突变基因A的患者倾向于临床轻型.IL-17F(rs763780,7488T/C)多态性与U C患者发病年龄之间有弱相关性,T/C基因型患者趋向于年轻型(P=0.046).结论:IL-17F rs763780基因多态性与CD易感性之间有弱相关性,在亚组分析中发现rs763780与CD的病变范围和UC的发病年龄有关.IL-17A rs2275913基因多态性与UC疾病严重程度呈负相关.     

Lamina propria and circulating interleukin-6 in newly diagnosed pediatric inflammatory bowel disease patients

OBJECTIVES: Understanding cytokine production patterns in early mucosal lesions of pediatric patients newly diagnosed with inflammatory bowel disease (IBD) may be critical to understanding IBD pathogenesis. Interleukin-6 (IL-6) has a central role in a multitude of immune system reactions; however, inconsistent lamina propria and serum IL-6 has been reported in IBD patients. Newly diagnosed pediatric IBD patients have not previously been evaluated for lamina propria or serum IL-6. METHODS: Serum and intestinal lamina propria biopsy whole organ culture supernatants were evaluated by ELISA for IL-6 obtained from newly diagnosed IBD patients, before initiation of immunomodulatory therapies. RESULTS: Levels of lamina propria IL-6 demonstrated significant correlation with graded severity of histological inflammation (p < 0.001). Log-transformed serum and organ culture IL-6 levels demonstrated significant correlation (p < 0.0001, R2 = 0.6226). Assigning a demarcation level of >400 pg/ml, serum IL-6 concentrations were a superior marker for the presence of microscopic intestinal inflammation than erythrocyte sedimentation rate (ESR), with a sensitivity of 82%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 82%. When evaluating subtypes of IBD, serum IL-6 levels were correlated more significantly with active disease in ulcerative colitis patients (p = 0.01, R2 = 0.74) than in Crohn's disease patients (p = 0.21, R2 = 0.33). CONCLUSIONS: This study outlines graded production of IL-6 in intestinal lamina propria and serum of newly diagnosed pediatric IBD patients, confirming the presence of IL-6 in early IBD patients. In addition, serum IL-6 may be a good predictor of IBD in pediatric patients with suspected or newly diagnosed IBD.     

Independent association between inflammatory markers (C-reactive protein, interleukin-6, and TNF-alpha) and essential hypertension

High blood pressure (HBP) has been associated with elevated C-reactive protein (CRP), a marker of chronic mild inflammation. However, the association between HBP and other inflammatory markers, particularly interleukin 6 (IL-6) and tumour necrosis alpha (TNF-alpha), has not been evaluated in well-controlled studies. We examined the cross-sectional relationship between IL-6, TNF-alpha, and CRP and HBP in a random sample of 196 healthy subjects. All markers were measured in duplicate with high-sensitivity ELISA tests. Three blood pressure (BP) measurments were averaged for the analysis, and subjects with systolic BP >or=140 and/or diastolic BP >or=90 mmHg were considered hypertensive. Log binomial regression was used to estimate multivariate-adjusted prevalence ratios (PR) of HBP. Of the subjects, 40% (79) were hypertensive (mean age: 44 years; range 30-64). After adjustment for age, sex, body mass index, family history of HBP, and the level of the other inflammatory markers, subjects in the second (PR: 3.10, P=0.003), third (PR: 2.32; P=0.031), and fourth quartiles (PR: 2.30; P=0.036) of IL-6 were more than twice as likely to be hypertensive than those in the first quartile. Corresponding PR estimates for TNF-alpha levels were 1.41 (P=0.014) for the second; 1.59 (P=0.001) for the third; and 1.61 (P=0.025) for the fourth quartile. The CRP-HBP association was not statistically significant. Our results suggest that TNF-alpha and IL-6 could be independent risk factors for HBP in apparently healthy subjects. Nevertheless, the temporal relationship between elevated inflammation markers and HBP should be ascertained in prospective cohort studies.     

Intestinal interleukin-13 in pediatric inflammatory bowel disease patients

BACKGROUND: Interleukin-13 (IL-13) is a multifunctional cytokine whose net principle action is to diminish inflammatory responses. Dysregulation of IL-13 production has been proposed to contribute to intestinal inflammation in inflammatory bowel disease (IBD) patients. Previous studies implicate IL-13 in IBD pathogenesis; however, they fail to accurately reflect in vivo intestinal IL-13 production. We evaluate IL-13, IL-6, and IL-1beta elaborations from colonic organ cultures of pediatric IBD patients METHODS: Endoscopic lamina propria biopsies or surgical specimens from pediatric patients with IBD were organ cultured and supernatants evaluated by enzyme-linked immunosorbent assay for IL-1beta, IL-6, and IL-13. RESULTS: IL-13 concentrations were significantly reduced in ulcerative colitis (UC) patients when compared with normal controls (P = 0.002) and Crohn disease (CD) patients (P = 0.001). End-stage UC patients at colectomy had lower intestinal IL-13 production than all other UC patients (P = 0.002). No significant correlation was found between IL-13 concentration and histologic disease severity (P = 0.134). CONCLUSIONS: Diminished intestinal IL-13 production is present in UC patients and wanes further with clinical disease progression. These findings suggest that UC patients may be differentiated from CD patients by intestinal IL-13 quantitation, and UC patients may benefit from IL-13 enhancing therapies.     

Saliva Interleukin-6 in patients with inflammatory bowel disease

OBJECTIVE: The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions that affect the gastrointestinal tract. In regulation of this inflammatory process, Interleukin-6 (IL-6) has a major role. Overproduction of IL-6 by immunocompetent cells contributes to development of the inflammatory condition. Elevated levels of IL-6 in saliva could be expected, because the saliva-producing cells are part of the digestive system. MATERIAL AND METHODS: IL-6 concentrations in saliva and plasma were studied in patients with CD (n=15), UC (n=7) and reference persons (RP) (n=19) by use of an ELISA method. RESULTS: A significant difference in saliva IL-6 concentration between CD patients (median 16.9 ng/L; p<0.05) and RP (median 6.3 ng/L) was found. A significant difference in plasma IL-6 concentration between CD (median 10.3 ng/L; p<0.001) or UC (median 7.8 ng/L; p<0.001) and RP (median 0.8 ng/L) was observed. In patients with CD, plasma IL-6 correlated significantly with C-reactive protein (CRP) as well as albumin. In patients with UC, saliva IL-6 and plasma IL-6 correlated significantly with AI (activity index) scores as well as albumin. In patients with UC, a significant correlation between the saliva and plasma IL-6 concentrations was found. CONCLUSIONS: IL-6 was found in saliva in patients with IBD, documenting the general involvement of the gastrointestinal tract extending to the mouth cavity, and measuring IL-6 may be an additional method for evaluating and monitoring the disease activity.     

Saliva Interleukin-6 in patients with inflammatory bowel disease

Objective. The inflammatory bowel diseases (IBD), Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory conditions that affect the gastrointestinal tract. In regulation of this inflammatory process, Interleukin-6 (IL-6) has a major role. Overproduction of IL-6 by immunocompetent cells contributes to development of the inflammatory condition. Elevated levels of IL-6 in saliva could be expected, because the saliva-producing cells are part of the digestive system. Material and methods. IL-6 concentrations in saliva and plasma were studied in patients with CD (n=15), UC (n=7) and reference persons (RP) (n=19) by use of an ELISA method. Results. A significant difference in saliva IL-6 concentration between CD patients (median 16.9 ng/L; p<0.05) and RP (median 6.3 ng/L) was found. A significant difference in plasma IL-6 concentration between CD (median 10.3 ng/L; p<0.001) or UC (median 7.8 ng/L; p<0.001) and RP (median 0.8 ng/L) was observed. In patients with CD, plasma IL-6 correlated significantly with C-reactive protein (CRP) as well as albumin. In patients with UC, saliva IL-6 and plasma IL-6 correlated significantly with AI (activity index) scores as well as albumin. In patients with UC, a significant correlation between the saliva and plasma IL-6 concentrations was found. Conclusions. IL-6 was found in saliva in patients with IBD, documenting the general involvement of the gastrointestinal tract extending to the mouth cavity, and measuring IL-6 may be an additional method for evaluating and monitoring the disease activity.     

Local and systemic interleukin-18 and interleukin-18-binding protein in children with inflammatory bowel disease

BACKGROUND: Interleukin-18 (IL-18) is increased in the inflamed mucosa of patients with Crohn's disease (CD). The balance between this pleiotropic proinflammatory cytokine and its natural inhibitor, IL-18-binding protein (IL-18BP), may contribute to the pathogenesis of inflammatory bowel disease (IBD). METHODS: Serum and mucosal biopsies were collected from children with IBD, from children with celiac disease, and from controls. Biopsies were maintained in culture for 24 hours, and supernatant was collected. Serum and supernatant IL-18 and IL-18BPa concentrations were measured by immunoassay. Disease activity score (PCDAI) and standard serum inflammatory markers (albumin, platelets, ESR, and CRP) were recorded. RESULTS: Serum IL-18 was greater in children with CD (537 pg/mL) than in controls (335 pg/mL; P < 0.05) but not in children with ulcerative colitis (UC) or IBD type unclassified (IBDU). Mucosal IL-18 was greater in children with CD and UC/IBDU than in controls (P < 0.01). Serum IL-18BPa was increased in children with CD compared with that in controls (3.9 versus 2.6 ng/mL; P < 0.05), but was not elevated in children with UC/IBDU. Furthermore, calculated free-serum IL-18 was elevated in CD, but not UC/IBDU, compared with that in controls (P = 0.001). Total and free-serum IL-18 were elevated in severe CD relative to in mild/moderate disease. CONCLUSIONS: IL-18, produced in the colons of children with IBD, may contribute to local inflammatory changes. Systemic IL-18 level may be a useful indicator of gut inflammation. Furthermore, free IL-18 is greatly elevated in children with CD, suggesting that compensatory increases in IL-18BPa are insufficient. Further exploration of the role of this cytokine in the pathogenesis of IBD is now required.