Serum trefoil factors in patients with inflammatory bowel disease

BACKGROUND: Trefoil factors (TFF1-3) play a critical role in mucosal protection and repair in the gastrointestinal tract. The aims of the present study were to examine associations between serum TFF1-3 and clinical and biochemical markers reflecting disease activity and to examine changes in TFF1-3 in patients with inflammatory bowel disease (IBD) before and during high-dose prednisolone treatment and tapering. METHODS: Serum concentrations of TFF1-3 were quantified in 48 ulcerative colitis (UC) and 50 Crohn's disease (CD) patients with little or moderate activity. Additionally, serum TFF concentrations were determined in patients with severe activity in colon IBD (4 UC and 6 CD) before and during prednisolone treatment with 7 healthy subjects as controls. RESULTS: Median concentrations of TFF1, TFF2, and TFF3 were significantly increased in IBD patients compared with healthy controls (p < 0.01). TFF3 concentrations correlated with clinical and biochemical parameters of disease activity in UC patients. In addition, a trend towards reduction in TFF concentrations during treatment with prednisolone and concomitant clinical and biochemical remission was observed. CONCLUSIONS: The present data support the concept that trefoil peptides are upregulated and may play a role in IBD mucosal protection and repair. In UC patients, TFF3 levels were increased in active disease levels correlated with disease activity indices. Due to a large variation, serum TFFs are not a potential marker for disease activity.     

Urotensin II levels in patients with inflammatory bowel disease

BACKGROUNDPatients with inflammatory bowel disease (IBD) are associated with increased cardiovascular risk and have increased overall cardiovascular burden. On the other hand, urotensin II (UII) is one of the most potent vascular constrictors with immunomodulatory effect that is connected with a number of different cardiometabolic disorders as well. Furthermore, patients with ulcerative colitis have shown increased expression of urotensin II receptor in comparison to healthy controls. Since the features of IBD includes chronic inflammation and endothelial dysfunction as well, it is plausible to assume that there is connection between increased cardiac risk in IBD and UII.AIMTo determine serum UII levels in patients with IBD and to compare them to control subjects, as well as investigate possible associations with relevant clinical and biochemical parameters.METHODSThis cross sectional study consecutively enrolled 50 adult IBD patients (26 with Crohn’s disease and 24 with ulcerative colitis) and 50 age and gender matched controls. Clinical assessment was performed by the same experienced gastroenterologist according to the latest guidelines. Ulcerative Colitis Endoscopic Index of Severity and Simple Endoscopic Score for Crohn’s Disease were used for endoscopic evaluation. Serum levels of UII were determined using the enzyme immunoassay kit for human UII, according to the manufacturer’s instructions.RESULTSIBD patients have significantly higher concentrations of UII when compared to control subjects (7.57 ± 1.41 vs 1.98 ± 0.69 ng/mL, P < 0.001), while there were no significant differences between Crohn’s disease and ulcerative colitis patients (7.49 ± 1.42 vs 7.65 ± 1.41 ng/mL, P = 0.689). There was a significant positive correlation between serum UII levels and high sensitivity C reactive peptide levels (r = 0.491, P < 0.001) and a significant negative correlation between serum UII levels and total proteins (r = -0.306, P = 0.032). Additionally, there was a significant positive correlation between serum UII levels with both systolic (r = 0.387, P = 0.005) and diastolic (r = 0.352, P = 0.012) blood pressure. Moreover, serum UII levels had a significant positive correlation with Ulcerative Colitis Endoscopic Index of Severity (r = 0.425, P = 0.048) and Simple Endoscopic Score for Crohn’s Disease (r = 0.466, P = 0.028) scores. Multiple linear regression analysis showed that serum UII levels retained significant association with high sensitivity C reactive peptide (β ± standard error, 0.262 ± 0.076, P < 0.001) and systolic blood pressure (0.040 ± 0.017, P = 0.030).CONCLUSIONIt is possible that UII is involved in the complex pathophysiology of cardiovascular complications in IBD patients, and its purpose should be investigated in further studies.     

Serum lipopolysaccharide-binding protein in endotoxemic patients with inflammatory bowel disease

BACKGROUND: In inflammatory bowel disease (IBD), enhanced inflammatory activity in the gut is thought to increase the risk of bacterial translocation and endotoxemia. By searching for signs of endotoxin-signaling cascade activation, including augmented levels of endotoxin, lipopolysaccharide-binding protein (LBP), and soluble CD14 receptor (sCD14), this prospective study sought to establish whether endotoxemia could contribute to greater clinical activity of disease. METHODS: Concentrations of plasma endotoxin, LBP, sCD14, several cytokines, acute phase proteins and clinical activity indices were determined in 104 patients with Crohn's disease (CD) and 52 patients with ulcerative colitis (UC). RESULTS: Endotoxemia was present in 48% of the patients with CD and in 28% of the patients with UC. The mean LBP was higher in patients with active CD (23.1 +/- 13.7 microg/mL) and UC (21.4 +/- 10.9 microg/mL) than in healthy controls (7.2 +/- 1.8 microg/mL; P < 0.01). Elevated serum concentrations of endotoxin and LBP were even detected in patients with inactive CD. Among the patients with active IBD, those with higher endotoxin levels had the worst clinical activity scores and the highest LBP levels. Treatment normalized LBP concentrations, from 29.1 +/- 13.0 to 15.2 +/- 7.3 microg/mL; (P < 0.05) in active CD and from 21.7 +/- 9.8 to 13.6 +/- 5.7 microg/mL; (P < 0.01) in active UC, along with normalizing endotoxin and sCD14 plasma concentrations. CONCLUSIONS: Patients with IBD show increased serum levels of endotoxin, LBP and sCD14. This alteration correlates with disease activity, with normal levels recovered after treatment, although less completely in Crohn's disease, and parallels a rise in proinflammatory cytokines, suggesting a contribution of bacterial products to the inflammatory cascade in these patients.     

High plasma osteopontin levels in patients with inflammatory bowel disease

BACKGROUND: Osteopontin (OPN) plays a key role in the progression of T(H)1-immune-mediated disease in models of multiple sclerosis and rheumatoid arthritis. AIM: To determine whether plasma OPN levels in patients with inflammatory bowel disease are associated with disease activity. METHODS: Plasma samples were obtained from patients with ulcerative colitis (UC, n=30), Crohn's disease (CD, n=30), and healthy volunteers (controls, n=30) and enzyme immunoassay was performed. RESULTS: Plasma OPN concentrations were significantly higher in patients with Crohn's disease than in controls (951.9+/-538.5 ng/mL and 659.0+/-163.7 ng/mL, respectively). OPN concentrations in patients with UC were also higher than in the controls (1149.6+/-791.0 and 659.0+/-163.7, respectively). There was a significant difference in plasma OPN level between active UC and inactive UC (2102.0+/-552.8 and 649.4+/-313.0, respectively). Moreover, a significant correlation was observed between plasma OPN concentration and disease activity, as determined by the clinical activity index in patients with UC. CONCLUSIONS: Our results indicate that the plasma concentrations of OPN are elevated in patients with UC and that OPN expression is correlated with clinical activity. These results provide insight into UC pathogenesis and suggest that OPN may be a useful tool for assessing disease activity.     

Elevated serum eotaxin levels in patients with inflammatory bowel disease

OBJECTIVE: Eotaxin is a recently characterized chemokine with potent and selective chemotactic activity for eosinophils. Previous studies indicating that eosinophils accumulate and become activated in inflammatory bowel disease (IBD) led us to hypothesize that eotaxin is potentially involved in the pathophysiology of IBD and, therefore, that eotaxin would be increased in the serum of patients with IBD. The objective of this study was to test those assumptions. METHODS: We investigated 72 patients with IBD, 35 with ulcerative colitis, and 37 with Crohn's disease. A total of 27 patients had active and 45 inactive disease; 26 were receiving corticosteroids. Eotaxin serum levels were determined by solid phase sandwich ELISA. Lymphocytes, monocytes, and granulocyte subpopulations were determined in fresh blood samples with an automated autoanalyzer. RESULTS: Serum eotaxin levels were significantly higher in patients with Crohn's disease and in those with ulcerative colitis than in the control subjects (p < 0.0001). Patients with inactive Crohn's disease had significantly higher levels of eotaxin than patients with inactive ulcerative colitis (p < 0.05). We did not find significant differences for activity or inactivity of disease, nor for treatment with prednisone. A negative correlation (p < 0.05) was found between eotaxin serum level and eosinophil counts in peripheral blood in patients with Crohn's disease. CONCLUSIONS: There is an increased expression of eotaxin in IBD patients, suggesting that eotaxin may be involved in the pathogenesis of IBD. This increase is more accentuated in Crohn's disease and negatively correlates with the eosinophil number in peripheral blood. Our data support the increasing evidence that eosinophil are functionally involved in the pathophysiology of IBD.     

Elevated thrombopoietin serum levels in patients with inflammatory bowel disease

OBJECTIVES: Elevated platelet count is a well recognized marker of inflammatory bowel disease (IBD) activity. Thrombopoietin (TPO) is a critical cytokine in the physiological regulation of thrombopoiesis. The aim of this study was to investigate the serum levels of endogenous TPO in patients with IBD, the relationship between platelet counts and TPO levels, and the correlation of TPO with the clinical characteristics of the patients. METHODS: TPO levels in 40 patients with Crohn's disease (CD), 63 patients with ulcerative colitis (UC), and in 42 healthy blood donors were assessed by ELISA. Platelet and white blood cell counts as well as C-reactive protein, and erythrocyte sedimentation rate were measured. RESULTS: TPO levels were significantly elevated in patients with CD (mean 124.3 +/- SD 58.0 pg/ml, p < 0.0001) and in patients with UC (mean 152.2 +/- SD 142.3 pg/ml, p < 0.0001), compared to controls (mean 53.4 +/- SD 45.7 pg/ml). TPO levels remained significantly elevated in remission (mean 144.7 +/- SD 131.1 pg/ml, p < 0.0001 compared to controls). Platelets were significantly elevated only in active CD, being normal in inactive disease as well as in all patients with UC. There was no significant correlation between TPO levels and various clinical characteristics of patients with IBD. No significant correlation was found between TPO levels and either platelet counts or white blood cell counts, erythrocyte sedimentation rate, and C-reactive protein. CONCLUSIONS: TPO levels are increased in IBD, irrespective of disease activity, platelet counts, and clinical characteristics of the patients. These observations indicate that TPO, apart from being a platelet producer, might have additional functions, probably related to the procoagulant state of IBD.     

Serum von Willebrand factor levels in patients with inflammatory bowel disease are related to systemic inflammation

BACKGROUND: Increased levels of circulating von Willebrand factor (vWF) have been found in patients with inflammatory bowel disease (IBD); this increase may reflect either endothelial damage or systemic inflammation. Our aim was to evaluate serum vWF levels in patients with IBD and their correlation with clinical and biochemical disease activity. METHODS: We evaluated serum vWF levels in 32 patients with ulcerative colitis (UC) (10 active with increased acute-phase reactants (APR), 6 active with normal APR, 16 in remission), 27 with Crohn disease (CD) (10 active, 12 quiescent, and 5 quiescent with increased APR), and 31 healthy controls. RESULTS: Mean levels of vWF were 100.1 (standard deviation (s), 51.4) in IBD and 89.9 (s, 36.9) in controls (P = 0.33). Only five (8.47%) patients (three with active UC, one with active CD, and one with inactive CD but increased APR) showed circulating vWF levels higher than the upper limit of normal (150), compared with 1 (3.2%) of controls (P = 0.32). Among CD patients vWF levels were 80.0+/-25.4 in patients with quiescent disease and normal APR, 123.3+/-63.4 in patients with active disease (P = 0.04 versus inactive with normal APR), and 135.8+/-90.0 in patients with quiescent disease and increased APR (P = 0.059 versus inactive with normal APR). Among UC patients vWF levels were 82.7+/-35.6 in patients with quiescent disease and normal APR and 125.1+/-54.2 in those with active disease and increased APR (P = 0.002). Overall, mean vWF levels were significantly higher in patients with increased APR than in patients with normal APR (P = 0.0005) and controls (P = 0.009). CONCLUSIONS: Our data show slight but significant increases in serum vWF levels in patients with IBD, which are correlated with signs of systemic inflammation.     

Serum gastrin levels in patients with thyroid dysfunction

Fasting serum gastrin levels measured by radioimmunoassay were found to be elevated in patients with hyperthyroidism and low in patients with hypothyroidism. The oral administration of beef extracts resulted in more increase of serum gastrin in hyperthyroid patients than in normal subjects. After restoration of the euthyroid state by treatment, no more increase in serum gastrin levels was observed. Slight correlation between gastrin levels and serum T3 levels was observed in pretreated hyperthyroid patients (r = 0.40), but significant correlation between them was found after restoration of the euthyroid state by treatment (r = 0.50). However, it seemed to be able to divide into two groups in the pretreated patients. One was a patient group whose gastrin levels correlated closely to serum T3 levels (r = 0.83, p less than 0.01). The other was a group whose serum gastrin levels remained in low even in high T3 levels (r = 0.81, p less than 0.01). Different sensitivity to thyroid hormone in the G-cells of gastrointestinal tract may exist in these two groups, because patients age and duration of their illness were not different between them.     

Serum hepcidin concentrations correlate with ferritin in patients with inflammatory bowel disease

Background and aimsAnemia is a frequent complication of inflammatory bowel disease (IBD). Hepcidin, a key mediator in this anemia, is up-regulated by high iron levels and inflammation, and serum levels are elevated in IBD. However, the extent of inflammatory activity and iron deficiency for the regulation of hepcidin is not known. This study aimed to evaluate serum hepcidin levels in anemic and non-anemic IBD patients, with iron or non-iron deficiency, and active or inactive disease.MethodsThis retrospective, observational study analyzed serum hepcidin levels from 247 patients with IBD (130 Crohn's patients and 117 with ulcerative colitis) recruited at Swiss Inflammatory Bowel Disease Cohort Study centers. Patients were divided into 5 different groups using criteria of active and inactive diseases (C-reactive protein, and CDAI/MTWAI = disease activity-index), anemia (hemoglobin) and iron deficiency (ferritin) and compared to healthy controls with no signs of anemia and normal ferritin levels. Hepcidin was measured using enzyme-linked immunosorbent assay.ResultsIndependent of inflammatory activity, all patients with decreased ferritin (< 30 μg/L) had significantly lower hepcidin levels when compared to patients and healthy controls having normal ferritin (> 30 μg/L). A significant correlation between serum ferritin levels and serum hepcidin was found (Spearman's Rho = 0.491; p < 0.001). A backward multi-linear stepwise regression analysis showed that only ferritin, and none of the inflammatory markers or age and sex correlated significantly (p = 0.005) with hepcidin.ConclusionThis retrospective analysis suggests that iron deficiency is the key trigger for hepcidin regulation in IBD patients with anemia.     

Increased serum levels of eotaxin in patients with inflammatory bowel disease

BACKGROUND: The CC-chemokines eotaxin and eotaxin-2, produced by epithelial and phagocytic cells, are potent and selective chemoattractants for eosinophils and basophils. The eosinophil is a potent inflammatory cell thought to play an important role in the pathogenesis of inflammatory bowel disease (IBD). In this study we investigated the serum concentrations of eotaxin and eotaxin-2 in patients with Crohn disease and ulcerative colitis. METHODS: Thirty-one patients with Crohn disease, 35 patients with ulcerative colitis and 41 control patients were studied. Eotaxin and eotaxin-2 serum levels were measured with solid phase sandwich enzyme-linked immunosorbent assays. RESULTS: Significantly increased serum eotaxin levels were observed in both patients with Crohn disease (289.4+/-591.5 pg/ml) and ulcerative colitis (207.0+/-243.4 pg/ml) when compared with controls (138.0+/-107.8 pg/ml) (P < 0.01). Moreover, patients with active Crohn disease and ulcerative colitis showed significantly higher serum eotaxin levels than patients with quiescent disease (434.0+/-776.8 pg/ml versus 113.8+/-65.4 pg/ml in Crohn disease and 295.7+/-337.1 versus 121.2+/-91.9 pg/ml in ulcerative colitis, P < 0.05). In contrast, there was no significant difference in eotaxin-2 serum levels among patients with Crohn disease (863.5+/-448.2 pg/ml), ulcerative colitis (1028.3+/-431.4 pg/ml) and controls (981.4+/-539.4 pg/ml). CONCLUSIONS: Eotaxin is significantly increased in serum of patients with active Crohn disease and ulcerative colitis, suggesting that this cytokine may play a role in the pathogenesis of IBD.     

Serum adipokines in inflammatory bowel disease

AIM:To investigate serum adipokine levels in inflammatory bowel disease(IBD)patients before treatment and after achieving clinical remission.METHODS:Serum concentrations of six adipokines(tissue growth factor-β1,adiponectin,leptin,chemerin,resistin,and visfatin)were studied in 40 subjects with active IBD[24 subjects with Crohn’s disease(CD)and in 16 subjects with ulcerative colitis(UC)]before and after three months of therapy with corticosteroids and/or azathioprine.Clinical diagnoses were based on ileocolonoscopy,computed tomography or magnetic resonance enterography and histological examination of mucosal biopsies sampled during endoscopy.Serum levels of adipokines were assessed by an indirect enzyme-linked immunosorbent assay.The control group was comprised of 16 age-and sex-matched healthyvolunteers.RESULTS:Baseline leptin concentrations were significantly decreased in both types of IBD compared to controls(8.0±9.1 in CD and 8.6±6.3 in UC vs 16.5±10.1 ng/mL in controls;P<0.05),and significantly increased after treatment only in subjects with CD(14.9±15.1 ng/mL;P<0.05).Baseline serum resistin concentrations were significantly higher in CD(19.3±12.5ng/mL;P<0.05)and UC subjects(23.2±11.0 ng/mL;P<0.05)than in healthy controls(10.7±1.1 ng/mL).Treatment induced a decrease in the serum resistin concentration only in UC subjects(14.5±4.0 ng/mL;P<0.05).Baseline serum concentrations of visfatin were significantly higher in subjects with CD(23.2±3.2ng/mL;P<0.05)and UC(18.8±5.3 ng/mL;P<0.05)than in healthy controls(14.1±5.3 ng/mL).Treatment induced a decrease in the serum visfatin concentrations only in CD subjects(20.4±4.8 ng/mL;P<0.05).Serum levels of adiponectin,chemerin and tissue growth factor-β1 did not differ between CD and UC subjects compared to healthy controls and also were not altered by anti-inflammatory therapy.Clinical indices of IBD activity did not correlate with adipokine levels.CONCLUSION:IBD modulates serum adipokine levels by increasing resistin and visfatin release and suppressing leptin production.     

Serum levels of gastrin in patients with colorectal neoplasia

Serum concentration of gastrin determined by radioimmunoassay in 90 consecutive patients who underwent colonoscopy, and serum levels of gastrin in patients with colorectal neoplasia and controls were compared. Based on clinical history, findings of colonoscopy, and pathologic examinations of biopsies, 80 patients were considered eligible for the study. Serum levels of gastrin in 36 controls were 54.1 +/- 13.1 pg/ml and did not differ from serum levels of gastrin in 44 patients with colorectal neoplasia. There was also no significant difference in serum levels of gastrin among 28 patients with adenomas and 16 patients with carcinoma. The present study disclosed that carcinogenesis of the colon and rectum was not associated with hypergastrinemia.     

Increased serum levels of YKL-40 in patients with inflammatory bowel disease

BACKGROUND AND AIMS: Initiation of a fibrotic process has been suggested as part of the intestinal response to chronic inflammation in inflammatory bowel disease. YKL-40 has been proposed as a new serum marker of fibrosis. We studied compared the serum levels of YKL-40 in patients with ulcerative colitis or Crohn's disease with inflammatory and healthy controls. PATIENTS AND METHODS: YKL-40 serum levels were measured in 179 patients with inflammatory bowel disease (94 ulcerative colitis, 85 Crohn's disease), in 23 with intestinal inflammation of other causes, and 70 matched healthy controls using a commercially available enzyme-linked immunosorbent assay. YKL-40 levels were assessed in terms of disease activity, type and localization. RESULTS: Mean serum YKL-40 levels were 102.6+/-82.7 ng/ml in ulcerative colitis patients and 112.2+/-83.7 ng/ml in Crohn's disease patients, significantly higher than in healthy controls (64.1+/-21.4 ng/ml) but not significantly different from inflammatory controls (77.8+/-23.1 ng/ml). Disease activity and C-reactive protein levels were significantly correlated with YKL-40 levels in both ulcerative colitis and Crohn's disease. Crohn's disease patients with ileum localization had significantly higher YKL-40 levels than those with ileocolonic or colonic disease. Patients with stenotic disease had mean YKL-40 levels not significantly different than those with nonstenotic disease. CONCLUSION: Serum levels of YKL-40 are increased in patients with inflammatory bowel disease, and this is associated with the inflammatory process rather than with the degree of fibrosis.     

Serum lysozyme in inflammatory bowel disease.

Serum lysozyme activity was measured in 18 patients with ulcerative colitis and 40 patients with Crohn's disease by both the turbidimetric and lysoplate method. Only one patient with ulcerative colitis and eight patients with Crohn's disease had increased serum lysozyme activity by either or both methods. Both methods appeared equally sensitive in detecting increased serum lysozyme activity. In Crohn's disease, the percent with elevated values increased with increase in disease activity.     

Serum lysozyme in inflammatory bowel disease.

The mean concentrations of serum lysozyme were markedly higher in patients with Crohn's disease and ulcerative colitis than in normal controls, and mean levels tended to be slightly higher in those with Crohn's disease than in those with colitis. The significance of these differences is unclear but the overlap between values in normal individuals and those with inflammatory bowel disease prevents the measurement having any discriminant value.