Intestinal inflammatory profile shows increase in a diversity of biomarkers in irritable bowel syndrome

Abstract

Background: It has been proposed that irritable bowel syndrome (IBS) is a low-grade mucosal inflammatory disease.

Objective: To characterize the intestinal inflammatory profile in IBS patients with or without fructose intolerance.

Design: Patients referred to colonoscopy with IBS complaints were screened for participation. IBS patients diagnosed according to the Rome II criteria and with no organic gastrointestinal disease were included in the study. One subgroup was patients included in a fructose-reduced diet study for 2 months with effects based on VAS symptom scores. Healthy controls were subjects under investigation of colorectal cancer screening with no IBS or other gastrointestinal diseases. All patients included had normal histology from rectum. Mucosal cytokines, chemokines and growth factors were measured by multiplex technology.

Results: Of 27 inflammatory markers tested in the mucosal tissue, 13 were significantly increased and none was significantly decreased in IBS as compared to controls. Significantly increased were the proinflammatory cytokines tumor necrosis factor, the typical TH1 markers IFNγ, IL-1β, IL-2 and RANTES, the typical TH2 markers IL-5 and IL-9, the TH17 marker IL-17, TNF, the pleiotropic IL-15, and the growth factors bFGF and GM-CSF. In IBS patients with fructose intolerance only IL-5 was significantly increased compared to patients without fructose intolerance.

Conclusions: A dysregulated mucosal inflammatory profile with an increased level of TH1, TH2 and TH17 markers, and growth factors were observed in bowel mucosa in of IBS patients when compared to healthy controls.     

Diagnostic yield of endoscopy in irritable bowel syndrome: A nationwide prevalence study 1987–2016

Introduction: Symptoms of irritable bowel syndrome (IBS) are common reasons for endoscopic procedures. We examined the yield of colonoscopy and upper endoscopy in IBS for several organic diseases.Methods: Matched population-based prevalence study in Sweden. We identified 21,944 participants diagnosed with IBS from 1987 to 2016 undergoing colonoscopy with a biopsy from all of Sweden's 28 pathology departments within 6 months of diagnosis. We compared prevalence of histopathology-proven diagnoses of inflammatory bowel disease (IBD), colorectal cancer, precancerous polyps, and microscopic colitis between patients recently diagnosed with IBS and matched controls without IBS (n = 81,101) undergoing colonoscopy. We also compared prevalence of celiac disease between patients diagnosed with IBS (n = 9,965) and matched controls (n = 45,584) undergoing upper endoscopy with biopsy. IBS patients were also compared to their siblings. Conditioned logistic regression estimated adjusted odds ratios (aORs).Results: Biopsy-proven IBD was seen in 1.6% of IBS and in 5.9% of controls (aOR=0.21; 95%CI=0.19–0.24). The prevalence of precancerous polyps was 4.1% vs. 13.0% (aOR=0.28; 95%CI=0.26–0.30), colorectal cancer 0.8% vs. 6.3% (aOR=0.17; 95%CI=0.14–0.20) and celiac disease 1.9% vs. 3.4% (aOR=0.54; 95%CI=0.47–0.63). Conversely, the prevalence of microscopic colitis was 2.9% vs. 1.7% (aOR=1.77; 95%CI=1.61–1.95), with higher prevalence in older patients and patients with IBS with diarrhea. Yield of colonoscopy for precancerous polyps, colorectal cancer, and microscopic colitis increased by age. Our findings were consistent using unaffected siblings as the comparator group.Discussion: The diagnostic yield of upper endoscopy and colonoscopy for organic disease is low in patients with a first-time diagnosis of IBS, though increases with age.     

Radiation exposure in patients with inflammatory bowel disease and irritable bowel syndrome in the years 2001–2011

Objectives: To compare cumulative ionizing radiation in patients with inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS) for the years 2001–2011. To study how radiation exposure change over time in patients with newly diagnosed IBD and factors associated with radiation exposure.

Material and methods: All radiological investigations performed between 1 January 2001 and 31 December 2011 were retrospectively recorded in patients with Crohn’s disease (CD) (n?=?103), ulcerative colitis (UC) (n?=?304) and IBS (n?=?149). Analyses were done with Mann–Whitney and Chi-Square test.

Results: The median total cumulative radiation exposure in mSv for CD (20.0, inter quartile range (IQR) 34.8), UC (7.01, IQR 23.8), IBS (2.71, IQR 9.15) and the proportion of patients who had been exposed for more than 50 mSv during the study period (CD 19%, UC 11%, IBS 3%) were significantly higher in the patients with CD compared to patients with UC (p?<?.001) and IBS (p?<?.001), respectively. In turn, patients with UC had significantly higher doses than patients with IBS (p?=?.005). Risk factors for radiation exposure were female gender (CD), early onset (UC), ileocolonic location (CD), previous surgery (CD and UC), depression (IBS) and widespread pain (IBS). In newly diagnosed CD, there was a significant decline in median cumulative radiation dose in mSv (17.2 vs. 12.0; p?=?.048) during the study period.

Conclusions: Patients with CD are at greatest risk for high cumulative radiation exposure, but there is a decline in exposure during the late 2000s. Non-colectomized patients with UC and patients with IBS have a relatively low risk of cumulative radiation exposure.     

Interleukin-18 is increased only in a minority of patients with active Crohn’s disease

Background and aims It has been suggested that Crohn’s Disease (CD) is associated with an elevated T helper 1 response as manifested by increased production of interleukin-18 (IL-18). Local concentrations of neutralizing IL-18 binding proteins (IL-18bp) may counteract biological functions of mature IL-18 in mucosal inflammation. Therefore, we investigated the IL-18/IL-18bp system in a large group of patients with active inflammatory bowel disease (IBD) to identify patients that could respond theoretically to IL-18 neutralizing treatment strategies. Patient/methods IL-18 and IL-18bp messenger RNA (mRNA) expression in colonic mucosa from patients with active CD (n = 72), active ulcerative colitis (UC; n = 32), and non-IBD controls (infectious colitis or diverticulitis; n = 19) and normal, non-diseased controls (n = 20) were measured by reverse-transcribed real-time polymerase chain reaction. Mature IL-18 protein and IL-18bp expression in inflamed mucosa were assessed by Western blotting. Results/findings Although IL-18 mRNA was increased in some patients with CD, the increase was not statistically significant. Densitometric evaluation of IL-18/α-actin ratio in patients with active CD (n = 20) and patients with UC (n = 10) demonstrated an increased ratio of IL-18 protein in CD when compared to UC (1.04 vs 0.72 [median]). On closer inspections, only 7/20 CD patients had an increased IL-18 protein expression in inflamed areas compared to noninflamed mucosa. Interpretation/conclusion IL-18 expression in active CD is heterogeneous, only a minority of patients expresses elevated levels. Further treatment strategies targeting IL-18 expression in active CD should be concentrated on this subgroup of patients.     

Proximal and distal gut hormone secretion in irritable bowel syndrome

Objective. Sensory and motor dysfunctions of the gut are both important characteristics of irritable bowel syndrome (IBS). Several gut peptides contribute to the regulation of gastrointestinal function but little is known about gut hormone secretion in IBS. Material and methods. We evaluated perceptual thresholds and fasting and postprandial plasma levels of proximal (cholecystokinin (CCK), motilin) and distal (peptide YY) gut peptides up to 1 h after ingestion of a high caloric meal in 99 IBS patients and 40 age- and gender-matched healthy controls. Results. Fasting plasma CCK levels were significantly elevated in patients (1.2±0.8 pM) compared with those in controls (0.8±0.7 pM, p=0.006), as was the incremental postprandial CCK response (72±73 versus 40±42 pM·60 min, respectively; p=0.003). No differences in fasting and postprandial motilin or PYY levels were found. The postprandial PYY response was significantly increased in hypersensitive compared to normosensitive patients (215±135 versus 162±169 pM, p=0.048). Patients with a diarrhoea predominant bowel habit had higher fasting motilin levels compared to constipated patients or alternating type IBS patients (82.1±36.5 versus 60.8±25.1 versus 57.5±23.9 pM, one-way ANOVA p=0.003). Conclusions. IBS patients have increased fasting and postprandial plasma levels of CCK. Changes in plasma levels of motilin and PYY may contribute to the clinical expression of IBS, such as the presence of visceral hypersensitivity or a predominant bowel habit.     

Contribution of monocytes Siglec-1 in stimulating T cells proliferation and activation in atherosclerosis

ObjectiveAtherosclerosis (AS) is widely accepted as an inflammatory disease and monocytes are particularly important in inflammatory immune responses. As an important biomarker of monocytes activation, Siglec-1 is highly expressed on circulating monocytes and atherosclerotic plaques of coronary artery disease (CAD) patients, but the exact role of Siglec-1 has not been elucidated.MethodsM-CSF, INF-α, IFN-γ, TNF-α and ox-LDL alone or in combination were used to stimulate Siglec-1 expression on monocytes, whereas small interfering RNA (si-RNA) or blocking antibody was used to down-regulate Siglec-1. Meanwhile, the role of Siglec-1 in chemokines secretion was determined. Then monocytes from CAD patients or healthy controls were cocultured with CD4+ or CD8+ T cells from a third healthy individual, and lymphocyte proliferation and activation were determined.ResultsAll the stimuluses could enhance Siglec-1 expression on monocytes in a dose-dependent manner, and M-CSF could synergistically stimulate Siglec-1 expression with ox-LDL. Moreover, the secretion of MCP-1, MIP-1α and MIP-2 were enhanced when Siglec-1 was up-regulated and down to normal level when Siglec-1 was blocked. More importantly, increased Siglec-1 expression on monocytes was related to the increased T cell proliferation and pro-inflammatory cytokines secretion in CAD patients. However, down-regulation of Siglec-1 could attenuate proliferation and activation of cocultured CD4+ and CD8+ T cells.ConclusionSiglec-1 can promote chemokines and pro-inflammatory cytokines secretion and influence the inflammatory process of AS.     

Pancreatic Polypeptide Secretion in Patients with Chronic Pancreatitis and After Pancreatic Surgery

Aim. We investigated polypeptide (PP) secretion under basal conditions, in response to bombesin infusion and to meal ingestion in patients with chronic pancreatitis (CP) and patients after different types of pancreatic surgery. Methods. Included were patients with CP without (n=20) and with (n=30) exocrine pancreatic insufficiency, patients after duodenum preserving resection of the head of the pancreas (DPRHP; n=20), after Whipple’s procedure (n=19), following distal pancreatectomy (DP; n=12), and healthy controls (n=36). Results. In CP patients basal and bombesin stimulated PP levels were significantly (p<0.01) reduced compared to controls only when exocrine insufficiency was present. Meal-stimulated PP secretion was significantly (p<0.01−0.05) reduced in CP patients both with and without exocrine insufficiency. Plasma PP peak increments after bombesin and meal ingestion correlated significantly with exocrine function. Basal PP, meal, and bombesin-stimulated PP secretion had low sensitivities of 22%, 42%, and 60% respectively, in detecting chronic pancreatitis. In patients after pancreatic surgery that included pancreatic head resection (DPRHP or Whipple operation) basal and stimulated PP secretion were significantly (p<0.01−0.05) reduced. Conclusion. Basal and meal or bombesin-stimulated PP levels are significantly reduced in patients with CP only when exocrine insufficiency is present. Determination of plasma PP levels has low sensitivity and is not useful in detecting chronic pancreatitis without exocrine insufficiency. In patients after pancreatic surgery, PP secretion is dependent on the type of operation (head vs tail resection).     

Symptoms in patients with ulcerative colitis in remission are associated with visceral hypersensitivity and mast cell activity

Abstract

Objective. Patients with ulcerative colitis in remission (UCR) frequently report irritable bowel syndrome (IBS)-like symptoms. Recent studies have pointed to the role of mast cells in mediating visceral hypersensitivity in IBS. We hypothesized that visceral hypersensitivity is frequently present in patients with UCR and is related to the quantity and activity of mast cells in the sigmoid mucosa. Material and methods. A group of 17 controls and 19 patients with UCR were studied. Rectal compliance and perception were measured by electronic barostat. Sigmoid biopsies were taken to quantify the amount of mast cells, degranulating mast cells and mast cells in close proximity to mucosal nerve endings. Results. Visceroperception significantly increased in UCR (p < 0.05) versus controls. Rectal perception correlated positively with IBS-like symptoms in UCR (r = 0.969; p < 0.05). The amount of mucosal mast cells (per 100 crypts) was significantly increased in UCR versus controls: 228 ± 20 versus 163 ± 18 (p < 0.05). In the UCR patients a higher percentage of mucosal mast cells was in close proximity to nerve endings (58 ± 4 vs. 38 ± 3% in controls; p < 0.05) or was degranulating (40 ± 7 vs. 16 ± 4% in controls; p < 0.05). There was a significant but weak correlation between quantity of mucosal mast cells and pain perception (r = 0.32; p < 0.05). Conclusion. Rectal hypersensitivity is associated with mucosal presence and activation of mast cells and with IBS-like symptoms in patients with UCR.     

In Vivo and protease-activated receptor-1-mediated platelet activation in patients presenting for cardiac catheterization

Pathways of platelet activation that are not targeted by current antithrombotic therapy may be crucial for the development of ischemic events in patients undergoing coronary angiography. We therefore investigated whether in vivo and thrombin receptor activating peptide (TRAP)-stimulated platelet activation and monocyte-platelet aggregate (MPA) levels can serve as independent risk markers for adverse outcomes in aspirin-treated patients presenting for cardiac catheterization. In vivo and TRAP-stimulated platelet surface P-selectin, activated glycoprotein IIb/IIIa (GPIIb/IIIa) and MPA levels were determined in 682 consecutive patients undergoing cardiac catheterization and in 47 healthy controls. Two-year follow-up data were obtained from 562 patients. In vivo platelet surface P-selectin, activated GPIIb/IIIa and MPA levels were significantly higher in patients with angiographically-proven coronary artery disease than in healthy controls (all p≤0.02). Patients with an acute coronary syndrome (ACS; n=125) had significantly higher levels of in vivo MPA than patients without ACS (n=437; p=0.01). In the overall study population (n=562) the surface expression of P-selectin and activated GPIIb/IIIa, and the levels of MPA in vivo and in response to TRAP were similar in patients without and with subsequent ischemic events (all p>0.05). Similar results were obtained when only patients with angiographically-proven coronary artery disease (n=459), stent implantation (n=205) or ACS (n=125) were analyzed. Receiver-operating characteristic curve analyses did not reveal cut-off values for P-selectin, activated GPIIb/IIIa, and MPA levels for the prediction of ischemic events. In conclusion, in vivo and TRAP-stimulated platelet activation and MPA levels did not predict adverse ischemic outcomes in aspirin-treated patients presenting for cardiac catheterization.     

Concomitant functional dyspepsia and irritable bowel syndrome decrease health-related quality of life in gastroesophageal reflux disease

Objective. Previous studies have reported an overlap between gastroesophageal reflux symptoms, functional dyspepsia (FD) and irritable bowel syndrome (IBS). The aim of this study was to investigate the prevalence of FD and IBS in gastroesophageal reflux disease (GERD) and the effect on health-related quality of life (HRQoL). Material and methods. FD and IBS prevalence and HRQoL were assessed by means of questionnaires in 215 referred and 48 non-referred (non-care-seeking) GERD patients, proven with 24-h pH-metry. HRQoL in 131 matched controls was used for comparison. Results. In this group of GERD patients 25% had FD (Dutch general population 13–14%), 35% had IBS (Dutch general population 0.6–6%) and 5% had both FD and IBS. Only 35% had neither FD nor IBS. Among referred GERD patients, the prevalence of FD and IBS was higher (p=0.002 versus non-referred). Compared with controls, GERD patients without FD/IBS had lower HRQoL scores on only one of the nine SF-36 subscales (p≤0.001); GERD+FD patients had lower scores on six subscales (p≤0.0005); GERD+IBS patients had lower scores on eight subscales (p <0.0005) and GERD+FD+IBS patients had lower scores on seven subscales (p≤0.001). Compared with patients with GERD only, GERD+FD patients had lower scores on five subscales (p≤0.001); GERD+IBS patients had lower scores on eight subscales (p <0.0005) and GERD+FD+IBS patients had lower scores on six subscales (p≤0.001). Conclusions. In patients with proven GERD, FD and IBS are more prevalent than in the general population. This prevalence is higher among care-seeking GERD patients. Only those GERD patients with concomitant FD/IBS have a much lower HRQoL. This suggests that in GERD, when properly treated, HRQoL is affected mainly by concomitant functional disorders and not by GERD itself.     

感染对IBS患者肠黏膜细胞因子表达的影响

目的:探讨感染对肠易激综合征(irritable bowel syndrome,IBS)患者神经-免疫-内分泌网络的影响.方法:感染后肠易激综合征(postinfectious irritable bowel syndrome,PI-IBS)患者45例,non-PI-IBS患者60例及30例对照者,结肠镜下活检回盲部黏膜标本,采用免疫组织化学法检测其肠黏膜SP、IL-2、IFN-γ、SPR与5-HT的表达,肥大细胞(mast cells,MC)采用甲苯胺蓝染色.结果:PI-IBS患者的SP表达分别高于non-PI-IBS与对照组(t=2.5,2.8,P<0.01);PI-IBS患者的MC表达分别高于non-PI-IBS与对照组(t=11.5,12.1,P<0.01).PI-IBS患者的5-HT表达分别高于non-PI-IBS与对照组(t=13.6,14.1,P<0.01);PI-IBS患者的SPR表达分别高于non-PI-IBS与对照组(t=3.8,6.1,P<0.05);PI-IBS患者的IFN-γ表达分别高于non-PI-IBS与对照组(t=13.8,15.2,P<0.05);PI-IBS患者的IL-2表达分别高于non-PI-IBS与对照组(t=12.6,14.7,P<0.05).PI-IBS患者回盲部黏膜MC和SP的表达呈高度正相关(r=0.71,P<0.01).PI-IBS患者回盲部黏膜5-HT和SPR的表达呈密切相关(r=0.18,P<0.05).IFN-γIL-2阳性表达的PI-IBS患者,SP表达高于非PI-IBS组(r=2.2,2.3,P<0.05)和对照组(t=2.3,2.4,P<0.05).结论:肠道感染后,神经纤维在IBS的免疫-神经-内分泌发生机制中的作用至关重要.     

Early inflammatory response in acute pancreatitis is little affected by body mass index

Objective. Obesity is a known risk factor for severe acute pancreatitis (AP), but the mechanism by which it affects the severity of AP is not fully understood. The main objective of this study was to investigate the relationship between obesity and inflammatory markers in AP. Material and methods. Thirty patients with AP who developed organ failure (Group I) and 87 patients with AP who survived without organ failure (Group II) were studied. Patients’ height and weight were measured at admission for calculation of body mass index (BMI). Blood samples were taken at admission for measurement of plasma interleukin (IL)-1β, IL-6, IL-10, IL-1 receptor antagonist, procalcitonin, C-reactive protein (CRP) and monocyte human leucocyte antigen (HLA)-DR expression. Results. Group I patients had higher BMI values (median 26.2 kg/m²) than Group II patients (25.2 kg/m²), p=0.033. Both CRP values and monocyte HLA-DR expression showed a significant correlation with BMI (Spearman's rank correlation r=0.32, p=0.003 and r=?0.33, p=0.002, respectively). The correlation between BMI and monocyte HLA-DR expression was significant in Group II patients (r=?0.34, p=0.002) but not in Group I patients (r=?0.02, p>0.05). There was no correlation between BMI and IL-1β, IL-6, IL-10, IL-1 receptor antagonist or procalcitonin. Conclusions. BMI did not affect either pro-inflammatory or anti-inflammatory cytokine levels in early AP. However, in patients with mild AP, BMI correlated positively with CRP levels and inversely with monocyte HLA-DR expression, which might reflect an amplified inflammatory response in these patients. Taken together, acute inflammatory response in AP, which ultimately determines the severity of AP, was little affected by BMI.     

Prevalencia de metanógenos y factores asociados en pacientes con síndrome de intestino irritable y controles sanos en una población del sureste de México

IntroductionMethane (CH₄) is an inert gas produced by colonic anaerobes and has been associated with different intestinal diseases, including irritable bowel syndrome (IBS). According to geographic region, the prevalence of methanogens varies, being higher in Africa (80%) and lower in the United States (35-40%). In Mexico, the prevalence of methanogens is unknown.AimTo evaluate the prevalence of CH₄ producers and associated factors in a group of patients with IBS and controls in a Mexican population.Materials and methodsA baseline fasting measurement of alveolar H₂ and CH₄ gas was carried out, by gas chromatography (stationary phase), in consecutive patients diagnosed with IBS and a control group. Subjects with baseline levels of H₂ of 0 ppm and CH₄ ≥ 5 ppm were classified as methanogenic.ResultsA total of 132 controls (53.8% women) and 67 patients with IBS (76% women) were included. The overall prevalence (n = 199) of methanogenic subjects was 38% (n = 76) (95% CI: 0.31-0.45) and they had a greater prevalence of overweight/obesity (56.5 vs 39.8%, P = .028). The prevalence of methanogens in the healthy controls was 41.6% (95% CI: 0.33-0.49), whereas, in the patients with IBS, it was 31.4% (n = 21, 71% IBS-C and 29% IBS-M).ConclusionsThe prevalence of methanogens in our study on a Mexican population was comparable to that reported in other populations and was associated with overweight/obesity. One-third of the patients with IBS presented with methanogens. Said microorganisms were particularly associated with the constipation-predominant IBS subtype.     

Low dose aspirin is associated with plasma chemerin levels and may reduce adipose tissue inflammation

Chemerin is a peptide chemoattractant for macrophages and an adipokine regulating adipocyte differentiation and metabolism. Plasma chemerin is increased in chronic inflammatory diseases and in obesity. As inflammation and obesity are risk factors for coronary artery disease (CAD), we investigated possible associations of plasma chemerin with inflammatory markers and atherosclerosis in a CAD case–control study (n = 470). Chemerin levels were associated with C-reactive protein, BMI and LDL levels, and negatively associated with HDL levels. Mean plasma chemerin levels were similar in controls and CAD patients but significantly higher in CAD patients not taking low dose aspirin. To investigate the mechanism of chemerin reduction by aspirin, we analyzed chemerin expression in hepatocytes and adipocytes treated with aspirin in the presence and absence of inflammatory cytokines. Chemerin expression was upregulated by pro-inflammatory stimuli in adipocytes but not in hepatocytes. Treatment of stimulated hepatocytes and adipocytes with aspirin did not affect chemerin expression. However, treatment of inflammatory M1 macrophages with aspirin reduced secretion of the pro-inflammatory cytokines IL-1β and IL-6, and increased secretion of the anti-inflammatory IL-10. In summary, we show that plasma chemerin levels are associated with markers of inflammation and that they are significantly higher in CAD patients not treated with low dose aspirin. In addition, we show that low dose aspirin treatment reduces pro-inflammatory cytokine secretion by macrophages, which may lead to reduced chemerin secretion by adipocytes and may be a reason for the lower chemerin levels in the circulation of CAD patients on low dose aspirin.     

Chromogranin A cell density in the large intestine of Asian and European patients with irritable bowel syndrome

Objective: Patients with irritable bowel syndrome (IBS) in Asia show distinctive differences from those in the western world. The gastrointestinal endocrine cells appear to play an important role in the pathophysiology of IBS. The present study aimed at studying the density of chromogranin A (CgA) cells in the large intestine of Thai and Norwegian IBS patients.

Methods: Thirty Thai IBS patients and 20 control subjects, and 47 Norwegian IBS patients and 20 control subjects were included. A standard colonoscopy was performed in both the patients and controls, and biopsy samples were taken from the colon and the rectum. The biopsy samples were stained with hematoxylin–eosin and immunostained for CgA. The density of CgA cells was determined by computerized image analysis.

Results: In the colon and rectum, the CgA cell densities were far higher in both IBS and healthy Thai subjects than in Norwegians. The colonic CgA cell density was lower in Norwegian IBS patients than in controls, but did not differ between Thai IBS patients and controls. In the rectum, the CgA cell densities in both Thai and Norwegian patients did not differ from those of controls.

Conclusions: The higher densities of CgA cells in Thai subjects than Norwegians may be explained by a higher exposure to infections at childhood and the development of a broad immune tolerance, by differences in the intestinal microbiota, and/or differing diet habits. The normal CgA cell density in Thai IBS patients in contrast to that of Norwegians may be due to differences in pathophysiology.     

Impaired counter-regulation of interleukin-1 by the soluble IL-1 receptor type II in patients with chronic liver disease

Objective. To assess the production of the endogenous IL-1 modulators IL-1 receptor antagonist (IL-1Ra), type I and II soluble IL-1 receptors (IL-1sRI and II) in patients with chronic liver disease (CLD). Material and methods. Plasma levels of IL-1beta (IL-1β) and IL-1 modulators were assessed in 126 CLD patients and 39 healthy controls. IL-1sRII was also measured in the supernatants of primary hepatocyte cultures. Results. Plasma IL-1sRI and IL-1Ra levels were significantly higher in cirrhotic CLD patients than in non-cirrhotic CLD patients and in controls. Levels did not depend on the etiology of CLD. Likewise, plasma IL-1β levels were elevated in CLD patients compared with those in controls. In contrast, IL-1sRII levels did not differ between CLD patients and controls. Cultures of human primary hepatocytes showed that IL-1sRII is induced by IL-1β, but not IL-6. Conclusions. In cirrhotic CLD patients elevated plasma IL-1β is not counteracted by endogenous levels of IL-1sRII, whereas high IL-1sRI is expected to neutralize the naturally occurring antagonist IL-1Ra, resulting in a dysregulation of the IL-1 system that might enhance pro-inflammatory activity of IL-1.     

Altered Expression of the Lymphocyte Activation Markers CD30 and CD27 in Patients with Pouchitis

Background: The mechanism underlying the development of ileal pouch inflammation in ulcerative colitis patients (pouchitis) after restorative proctocolectomy is unclear. Persistent systemic T cell activation or expansion of specific memory cell populations could predispose certain patients to develop local inflammation within the neo-rectum. Therefore, the aim was to study the expression of the lymphocyte activation markers CD27, CD30, CD25 and CD69 on the CD45RO+ memory cell subset of isolated peripheral blood mononuclear cells (PBMC), soluble CD30 levels and mucosal CD30 expression in patients with pouchitis and in controls. Methods: Flow cytometry was performed on PBMC isolated from patients with pouchitis (n = 9), without pouchitis (n = 10) and normal controls (n = 9). Serum CD30 was measured in patients with pouchitis (n = 25), without pouchitis (n = 26) and normal controls (n = 20) by ELISA. CD30 expression was quantified in pouchitis (n = 15) and normal pouch (n = 15) mucosa using a three-stage immunoperoxidase method. Results: Naïve CD45RO-CD27+ PBMC were significantly decreased in pouchitis (25.6%) compared to normal controls (34.4%), (P = 0.03). CD30, CD25 and CD69 subsets did not differ between the groups. Serum CD30 was increased in pouchitis patients 58 (1-380) U/ml compared to non-pouchitis 16.5 (1-290) U/ml, P = 0.007, and normal controls 11 (2-80) U/ml, P = 0.0005. In the mucosa, the numbers of CD30+ cells were increased in pouchitis compared to noninflamed pouches (P = 0.02). Conclusions: Increased sCD30 in pouchitis is associated with elevated mucosal expression. Of the activation markers studied, only the circulating naïve CD27+ population differed in pouchitis patients compared with controls. The observed decrease in this cell type may reflect antigen priming and subsequent loss of CD27 implying that antigen driven activation of specific T cell subsets may occur in pouchitis.