PMN-elastase in assessment of patients with inflammatory bowel disease

PMN-elastase is a proteinase released by activated neutrophils. PMN-elastase was determined in two independent populations with inflammatory bowel disease. In an unselected population of 70 consecutive patients with Crohn's disease and 24 patients with ulcerative colitis with different degrees of disease activity plasma PMN-elastase levels were statistically significantly higher in patients with active than in patients with inactive disease [Crohn's disease: 80.5±33.2 ng/ml vs 60.1±24.6 ng/ml (means±sd),P=0.0017; ulcerative colitis: 98.2±54.9 ng/ml vs 59.2±16.8 ng/ml,P=0.026]. PMN-elastase levels in feces were also higher in patients with active Crohn's disease (23.6±15.3 ng/g vs 13.6±12.5 ng/g,P=0.0021) and active ulcerative colitis (46.5±60.5 ng/g vs 20.2±25.0 ng/g,P=0.46), but the difference reached significance only in Crohn's disease. Correlation of disease activity and PMN-elastase in individual patients showed a statistically significant correlation between plasma and fecal elastase concentrations and disease activity in ulcerative colitis (plasma:r=0.72,P<0.001; feces:r=0.423,P<0.001) but not fecal elastase concentrations (r=0.0083,P=0.485) correlated significantly with disease activity. Plasma PMN-elastase correlated weakly with fecal PMN-elastase levels in Crohn's disease (r=0.431,P<0.01) and in ulcerative colitis (r=0.515,P=0.05). In 28 patients with highly active Crohn's disease [median severity activity index (SAI) 203] and 11 patients with highly active ulcerative colitis [median Rachmilewitz index (RI) 14] studied before and four weeks after steroid therapy, treatment lowered the median SAI to 140 and the median RI to 4.5. Mean plasma elastase concentrations decreased concomitantly from 83±44.9 ng/ml to 61.8±25.8 (P=0.0035) in patients with Crohn's disease and from 110±49.5 to 71.6±28.8 ng/ml (P=0.0069) in patients with ulcerative colitis. In conclusion, there is a release of PMN-elastase in active IBD, which can be detected in plasma as well as in feces. Plasma elastase levels reflect disease activity in patients with IBD. The variation of the data and the large overlap between different groups, however, strongly reduce the clinical value.This research was supported by the SFB 154 of the Deutsche Forschungsgemeinschaft. V. Gross is supported by a Heisenberg-Stipendium of the Deutsche Forschungsgemeinschaft.     

Adhesion molecules in inflammatory bowel disease.

The ability of leucocytes to adhere to endothelium is essential for leucocyte migration into inflammatory sites. Some of these adhesion molecules are released from the cell surface and can be detected in serum. The soluble adhesion molecules intercellular adhesion molecule 1 (ICAM-1), E selectin, and vascular cell adhesion molecule 1 (VCAM-1) were studied in the serum of patients with Crohn's disease, ulcerative colitis, and healthy controls. A second blood sample was taken from patients with active disease after one month of treatment and a third two months after remission was achieved. Tissue expression of the same adhesion molecules was studied by immunohistology. Circulating VCAM-1 concentrations were significantly higher in patients with active ulcerative colitis (n = 11, median = 165 U/ml) compared with patients with inactive ulcerative colitis (n = 10, median = 117 U/ml, p < 0.005), active Crohn's disease (n = 12, median = 124 U/ml, p < 0.02), and controls (n = 90, median = 50 U/ml, p < 0.0001). Within each disease group there were no significant differences in E selectin or ICAM-1 concentrations between the active and inactive states, however, patients with active Crohn's disease had significantly higher ICAM-1 concentrations (n = 12, median = 273 ng/ml) than controls (n = 28, median = 168, p < 0.003). VCAM-1 concentrations fell significantly from pretreatment values to remission in active ulcerative colitis (p < 0.01). In Crohn's disease there was a significant fall in ICAM-1 both during treatment (p < 0.01) and two months after remission (p < 0.02). Vascular expression of ICAM-1 occurred more often and was more intense in inflamed tissue sections from patients with ulcerative colitis and Crohn's disease than from controls. Vascular labelling with antibody to E selectin also occurred more often in patients with active inflammatory bowel disease. In conclusion, increased circulating concentrations of selected adhesion molecules are associated with inflammatory bowel disease. There is also evidence of local upregulation, particularly of ICAM-1. Differential expression of adhesion molecules in tissue may play a part in the initiation of leucocyte migration and local inflammation; the function of circulating adhesion molecules is unknown, but may play a physiological part in blocking adhesion.     

Circulating soluble vascular adhesion protein 1 in patients with inflammatory bowel disease

OBJECTIVE: A dysregulated local immune defence with a constant influx of leucocytes provides a basis for continuous intestinal inflammation in ulcerative colitis and Crohn's disease. Since vascular adhesion protein 1 (VAP-1) is one of the adhesion molecules that mediates lymphocyte binding to endothelium, we investigated the levels of soluble VAP-1 (sVAP-1) in the sera of inflammatory bowel disease (IBD) patients compared with healthy controls. METHODS: sVAP-1 serum levels were measured in 161 IBD patients (90 ulcerative colitis, 71 Crohn's disease) and 93 controls using a commercially available enzyme-linked immunosorbent assay (ELISA). sVAP-1 levels were correlated with disease activity and localization. In 42 patients, sVAP-1 levels were measured in both the active and inactive phases of the disease. RESULTS: sVAP-1 serum levels were detected in all control and IBD subjects. Mean sVAP-1 levels were 365.5 +/- 153.5 ng/ml in ulcerative colitis patients, 336.4 +/- 172.8 ng/ml in Crohn's disease patients, and 344.7 +/- 150.4 ng/ml in healthy controls. The differences between the groups were not significant. No association between disease activity or disease localization and sVAP-1 was found. CONCLUSIONS: sVAP-1 serum concentrations are not significantly different in IBD and healthy control subjects. sVAP-1 serum levels are of no value in the assessment of disease activity or severity of inflammation in patients with IBD.     

Circulating soluble intercellular adhesion molecule-1 (sICAM-1) in active inflammatory bowel disease

Intercellular adhesion molecule (ICAM)-1 promotes the initial interaction between macrophages and T cells during immune activation. We have measured serum levels of soluble ICAM-1 (sICAM-1) by ELISA in 27 patients with ulcerative colitis (UC), 31 with Crohn's disease (CD), and 29 healthy subjects. The median sICAM-1 serum concentration was significantly increased in inflammatory bowel disease (IBD) patients (355 ng/ml, range 195–855) compared to controls (245 ng/ml, 155–580) (P=0.001). Variance analysis for trend showed that sICAM-1 levels were significantly higher in patients with active CD and UC, compared to those with inactive disease and controls (P=0.00002). The concentration of sICAM-1 was higher in CD patients (365 ng/ml 230–470) compared to UC (300 ng/ml 195–855) (P=0.01). Furthermore, weak but significant correlations were found between serum levels of sICAM-1 and: soluble IL-2 receptors, orosomucoid, and C-reactive protein. It is suggested that increased circulating sICAM-1 levels may reflect increased adhesiveness and signal transmission across cells, probably as a result of shedding of the parent molecule during local cellular immuneresponsesin vivo.This study was supported by grants from Else & Mogens Wedell-Wedellsborg's Foundation, Direktør Jacob Madsen og hustru Olga Madsen's Foundation, and handelsgartner Ove Villiam Buhl Olesen and hustru Edith Buhl Olesen's Foundation.     

Serum gastrin levels in patients with inflammatory bowel disease

The aim of this study was to estimate the levels of serum gastrin in a group of patients with either ulcerative colitis or Crohn's disease and to compare the results with those of a group of normal controls. In 108 consecutive patients with IBD (66 with ulcerative colitis, 32 with Crohn's disease and 10 with indetermined colitis) serum levels of gastrin were measured by radioimmunoassay. One hundred and eight normal people were served as controls. The levels of serum gastrin were significantly elevated in patients with Crohn's disease compared to normal controls (74.4 +/- 43.9 pg/ml vs. 47.5 +/- 32.4 pg/ml, P<0.05), irrespectively of the activity of the disease. On the contrary, patients with ulcerative colitis exhibited no significant differences compared to normal controls. Differences between Crohn's disease and ulcerative colitis patients were statistically significant (P<0.001). The rate of infection by Helicobacter pylori in patients with inflammatory bowel disease was statistically significantly lower as compared with normal controls (31.7% vs. 55.1%, P<0.001). It is concluded that patients with active or inactive Crohn's disease have increased levels of serum gastrin. This may have implications concerning the high incidence of upper GI lesions found in patients with Crohn's disease despite the very low incidence of Helicobacter pylori infection.     

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.     

Inflammatory markers in a 2-year follow-up of coronary artery disease

Our study was designed in an attempt to determine the dynamics of changes in serum tumor necrosis factor (TNF)-α, soluble forms of its receptors (sTNFR 1, sTNFR 2), and adhesion molecules (sE-selectin, sP-selectin, sVCAM-1, sICAM-1) over a 2-year follow-up of patients with coronary artery disease (CAD). The study involved 70 patients with stable CAD (stable angina class II/III according to the Canadian Cardiovascular Society) and 20 apparently healthy subjects. Over the follow-up period a marked attenuation of angina (P < 0.001) was observed. Interventional treatment (percutaneous coronary intervention, coronary artery bypass grafting) was used in 53 CAD patients. Laboratory analysis revealed a significant decrease of serum TNF-α and sTNFR1 at 2 years (TNF-α: 12.1 ± 0.7 pg/ml; sTNFR 1: 1306 ± 46 pg/ml) as compared to baseline levels (16.5 ± 0.7 pg/ml, P = 0.030; 1551 ± 82 pg/ml, P = 0.048, respectively). The levels of sP-selectin (159 ± 7 vs 201 ± 14 ng/ml, P < 0.01) and sICAM-1 (133 ± 4 vs 153 ± 6 ng/ml, P < 0.05) were found to be significantly increased as compared to the baseline. Interventional procedures resulted in suppression of both cytokine (TNF-α, sTNFR 2) and adhesion molecule (sE-selectin, sP-selectin) activation in the CAD group. The baseline and post-follow-up TNF-α and sTNFR 1 levels showed persistent elevation in CAD patients as compared to the controls (9.0, 956.3 pg/ml, respectively; P < 0.01). There were no differences between baseline and final cytokines and adhesion molecules in healthy subjects. The course of CAD as modified by a clinically effective therapy is characterized by changes of immune markers activation. Revascularization seems to be an important factor suppressing both cytokine and adhesion molecule activation in CAD patients.     

Functional, morphological and biochemical study of the jejunal mucosa in cryptogenetic colitis

The function of the jejunum has been assessed in patients with ulcerative colitis (n = 23) and Crohn's disease of the colon (n = 20) by measurement of serum folate levels, oral folic acid and D-xylose absorption. Forty-six normal subjects served as controls. The mean serum folate level was 4.5 +/- 2.0 ng/ml in patients with the disease and 7.8 +/- 1.7 ng/ml in controls (p less than 0.001) and was similarly decreased in both ulcerative colitis and Crohn's disease patients. It was lower in patients under sulphasalazine therapy (n = 15) than in those untreated: 3.5 +/- 1.5 vs. 4.8 +/- 2.1 ng/ml (p less than 0.05). Serum folate correlated with disease activity in the latter only. The peak serum folate obtained during the oral absorption test was decreased in patients: 38.9 +/- 12.9 vs. 60.8 +/- 19.3 ng/ml in controls (p less than 0.001); this decrease was similar in ulcerative colitis and Crohn's disease, in treated and untreated patients and was independent of disease activity. Basal serum folate did not correlate with peak serum folate in any patient group. D-xylose absorption was normal in every case. Jejunal biopsies were performed in 23 patients, 13 of whom had folic acid malabsorption (13 with ulcerative colitis, 10 with Crohn's disease of the colon). The crypt height/villus height ratio was abnormal (greater than 0.6) in only 2 patients and borderline in 9 others. The fragility of enterocyte brush-borders and lysosomes, as assessed by biochemical methods, was normal in all cases.(ABSTRACT TRUNCATED AT 250 WORDS)     

Double Filtration Plasmapheresis Maintains Normal Adhesion Molecule Levels

Abstract: Levels of plasma soluble vascular cell adhesion molecule-1 (sVCAM-1), soluble intercellular adhesion molecule-1 (sICAM-1), and von Willebrand factor (vWF) increase in patients with peripheral vascular or ischemic heart disease. These factors are related to the progression of atherosclerosis. Furthermore, these substances and thrombomodulin (TM) are indicators for assessing the degree of damage to the endothelium. To evaluate the effect of double filtration plasmapheresis (DFPP) on these molecules, the plasma levels of vWF, sICAM-1, sVCAM-1, and TM were measured in 4 familial hypercholesterolemia (FH) patients who underwent treatment with DFPP at 2 week intervals for more than 3 years. The levels of sVCAM-1 and sICAM-1 in hypercholesterolemia patients with ischemic heart disease as a control was 773 ± 109 and 334 ± 82 ng/ml. These values were higher than the normal value. In the FH patients who underwent DFPP treatment, the average sICAM-1 levels were 221 ± 47 and 197 ± 36 ng/ml before and after, respectively. The average sVCAM-1 levels were 601 ± 87 and 486 ± 60 ng/ml. There were no significant differences between the pre- and post-DFPP values. The activities of plasma vWF before and after DFPP treatment were 158 ± 23 and 45 ± 9%. The levels of plasma TM before and after treatment were 3.0 ± 0.3 and 3.4 ± 0.5 FU/ml. From these results, it is suggested that DFPP treatment does not damage the endothelium and may prevent the progression of atherosclerosis by removing the substances that induce the production of sICAM-1 and sVCAM-1 due to long-term treatment.     

Mucosal glucosamine synthetase activity in inflammatory bowel disease

Abnormalities in colonic glycoprotein synthesis have been implicated in the pathogenesis of ulcerative colitis and Crohn's disease. Glucosamine synthetase is the rate-limiting step in the biosynthesis of gastrointestinal glycoprotein and has been measured in control subjects (N=23) and patients with ulcerative colitis (N=26) or Crohn's disease of the colon (N=20) classified according to the macroscopic status of the rectum. Glucosamine synthetase activity was relatively constant around the normal colon but lower levels were found in the terminal ileum. In ulcerative colitis, glucosamine synthetase activity was similar to controls (24.0±1.9) mmol/g wet (wt/hr) irrespective of disease activity (quiescent:N=13, =27.3±1.9; activeN=16, =26.2±2.3). Rectal glucosamine synthetase activity was normal in the presence of active Crohn's proctocolitis (29.4±3.1) but raised in patients with Crohn's colitis and rectal sparing (37.2±4.9P<0.02). Glucosamine synthetase activity was strongly influence by the degree of epithelial preservation.     

The levels of sCD30 and of sCD40L in a group of patients with systemic lupus erythematodes and their diagnostic value

CD30/CD30L and CD40/CD40L are molecules from the tumor necrosis factor (TNF) superfamily. They have a major effect on communications between the B and T cells, which leads to control of maturation, proliferation, and apoptosis of those cells. The aim of this study was to compare the levels of a soluble form of CD30 (sCD30) and a soluble ligand CD40 (sCD40L) in patients with systemic lupus erythematosus (SLE) (n=65) and healthy controls (sCD30 n=20, sCD40L n=10) with other parameters of SLE activity. Patients were divided into subgroups according to presence or absence of lupus nephritis (LN; 33 with LN, 32 without LN). The serum levels of selected parameters were assessed also in the subgroups with low active disease characterized by European Lupus Activity Measure (ECLAM) at most 3(n=29) and active disease with ECLAM more than 3 (n=36). The serum levels of sCD30 were 66.0±40.2 UI/ml in the whole group. The mean serum levels were 60.0±45.2 UI/ml in the subgroups with LN, 67.1±38.9 UI/ml in the subgroup without LN, 80.2±51.9 UI/ml in the subgroup with active disease, 55.4±24.1 UI/ml in the subgroup with low active disease, and finally, 40.1±19.2 U/ml in the controls. Significant differences were found between the SLE patients and controls (p=0.0001) and between the active and nonactive groups (p=0.002). A correlation was found between levels of CD30 and ECLAM (r=0.25, p≤0.05), SLEDAI (SLE Disease Activity Index) (r=0.25, p≤0.05), C4 component of the complement system (r=0.24, p=0.02), and anti-C1q antibodies (r=0.42, p=0.0001). The levels of sCD40L were 7.4±6.7 ng/ml in whole SLE group, 7.0±8.1 ng/ml in the subgroup with LN, 8.0±4.9 ng/ml in the subgroup without LN, 7.1±5.0 ng/ml in the group of patients with active disease, 7.73±7.8 ng/ml in the subgroup with low activity, and 2.96±1.39.0 ng/ml in the controls. The difference in sCD40L serum levels between patients with SLE and controls was statistically significant (p=0.02). A correlation was found with the anti-C1q antibodies (r=0.21, p=0.05); no other correlations were found. These findings indicate some potentional role of both serum parameters in measurement or SLE disease activity, although their usage in the diagnostic of disease requires further investigation.     

Serum lysozyme,serum proteins,and immunoglobulin determinations in nonspecific inflammatory bowel disease

The serum levels of lysozyme, serum electrophoresis, and serum immunoglobulins were determined prospectively in 101 patients with ulcerative colitis, ulcerative proctitis, Crohn's disease, or nonclassifiable nonspecific inflammatory bowel disease. Although the mean serum lysozyme concentration of patients with Crohn's disease (10.5±6.8 μg/ml) and ulcerative colitis (9.6±4.1 μg/ml) performed by a standardized lysoplate method was significantly greater than normal controls (6.0±1.5 μg/ml), the results did not correlate with the diagnosis nor with the degree of disease activity. Individually separated protein fractions and serum immunoglobulins also did not correlate with the serum lysozyme levels. This study indicates that measurement of the level of serum lysozyme in individual patients is not helpful in determining the cause or degree of activity of non-specific inflammatory bowel disease.     

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.     

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.     

Increased serum levels of granulocyte-macrophage colony-stimulating factor in hypercholesterolemic patients

Background: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that may be implicated in multicellular events of the atherosclerotic inflammatory process. Methods: To investigate the impact of hypercholesterolemia on serum levels of GM-CSF, we determined circulating GM-CSF, soluble intercellular adhesion molecule-1 (sICAM-1), and soluble vascular cell adhesion molecule-1 (sVCAM-1) in 25 hypercholesterolemic patients with no clinical evidence of cardiovascular disease and in 15 normocholesterolemic control subjects who were matched for age and sex to the hypercholesterolemic group. Results: Hypercholesterolemic patients had higher levels of GM-CSF than did controls (5.8±2.1 vs. 2.1±0.9 pg/ml, P<0.05). They also displayed increased serum levels of sICAM-1 (236.1±19.7 vs. 183.5±13.1, P<0.01) and of sVCAM-1 (673.8±27.3 vs. 591.3±23.4, P<0.01). A significant correlation was observed between GM-CSF levels and LDL-C values (r=0.58, P<0.01) as well as between GM-CSF and sICAM-1 levels (r=0.78, P<0.001). Conclusions: These results suggest that hypercholesterolemia is associated with elevated serum GM-CSF levels. The increased levels of circulating GM-CSF in hypercholesterolemic patients may be related to the monocyte/endothelial cell adhesive interaction and subsequent inflammatory process that accompany the hypercholesterolemia and characterize the early stages of atherogenesis.     

Role of soluble triggering receptor expressed on myeloid cells in inflammatory bowel disease

AIM: To investigate the probable role of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) in the pathogenesis of inflammatory bowel disease (IBD). METHODS: Fifty-eight patients were enrolled; nineteen healthy volunteers served as controls; 8 patients were diagnosed with Crohn's disease, and 31 with ulcerative colitis. Clinical and endoscopic activity indexes of patients with Crohn's disease and ulcerative colitis respectively were estimated. Upon admission blood was sampled; sTREM-1 and TNFαwere measured by an immunoassay and malondialdehyde (MDA) by the thiobarbitourate assay, after passage through an HPLC system. RESULTS: Median±SE of TNFαof controls, patients with Crohn's disease and patients with ulcerative colitis were 6.02±3.94, 7.98±5.08 (P = NS vs controls), and 8.45±4.15 ng/L (P = 0.018 vs controls) respectively. Respective values of sTREM-1 were 53.31±32.93, 735.10±197.17 (P = 0.008 vs controls) and 435.82±279.71 ng/L (P = 0.049 vs controls). sTREM-1 was positively correlated with Crohn's disease activity index and clinical and endoscopic activity indexes of ulcerative colitis (P = 0.002, 0.001 and 0.009, respectively). sTREM-1 of patients with ulcerative colitis was positively correlated with TNFa (P = 0.001). CONCLUSION: sTREM-1 seems to behave as a novel mediator in IBD in correlation with the degree of the inflammatory reaction of the intestinal mucosa.     

Influence of intestinal inflammation (IBD) and small and large bowel length on fecal short-chain fatty acids and lactate

Treatment with short-chain fatty acids (SCFAs) seems promising in ulcerative colitis and changes in colonocyte oxidation of butyrate have been suggested to be of importance for the development of this disease. The influence of small and large bowel length after surgery on SCFAs is only partly known. SCFAs and lactate were measured in consecutive fecal samples from 300 patients with ulcerative colitis (103), Crohn's disease (127), and noninflammatory bowel disease (70); 205 had had surgery, 52 had short bowels (<200 cm). Lactate (mainly thel-isomer) was elevated in ulcerative colitis patients with pancolitis (mean ±sem, 17±5 mmol/liter) and proctitis (12±3 mmol/liter) compared with quiescent ulcerative colitis (3±1 mmol/liter,P<0.01), and correlated with the index of Truelove (R=0.52,P<0.0005). Lactate was also increased in Crohn's colitis (21±8 mmol/liter), but not in isolated ileitis (4±2 mmol/liter), compared with quiescent Crohn's disease (7±2 mmol/liter,P<0.02), but did not correlate with the activity index (CDAI;R=0.18,P=0.12). In contrast to earlier reports, SCFAs (including butyrate) did not correlate with inflammatory activity or localization in either ulcerative colitis or Crohn's disease. The length of the small bowel had no influence on SCFAs and lactate in patients with either no colonic function (ileostomies), or with >50% and <50% preserved colorectal length, respectively. Fecal SCFAs from completely (100%) preserved large bowels (89±5 mmol/liter), and from>50% (76±7 mmol/liter) and<50% (72±7 mmol/liter) preserved colons were not significantly different, in contrast to SCFAs from ileorectals (51±10 mmol/liter), ileal reservoirs (57±6 mmol/liter), and ileostomies (20±2 mmol/liter). Fecal lactate is associated with proctocolitis, but not with ileitis. SCFAs were remarkably constant and not influenced by active inflammation in patients with inflammatory bowel disease or extreme differences in the length of the small or large intestine.     

Elevated Serum Vascular Endothelial Growth Factor in Children and Young Adults with Crohn's Disease

Vascular endothelial growth factor (VEGF) is acytokine released by fibroblasts, epithelial cells, andleukocytes that potentiates vascular permeability andgrowth of new capillaries. Because of these multiple effects, VEGF has been postulated to play arole in the pathogenesis of autoimmune disease, as wellas in wound healing. We hypothesized that VEGF waspotentially important in mediating the vascularpermeability and angiogenesis seen in Crohn's disease, andtherefore that VEGF would be increased in the serum ofchildren with Crohn's disease. Serum was obtained from73 children and young adults with Crohn's disease, 47 with ulcerative colitis, and 29 controls.VEGF levels were measured by enzyme-linked immunosorbentassay. Mean VEGF levels were significantly higher inpatients with Crohn's disease (436.4 ± 37.2pg/ml) than in ulcerative colitis (306 ± 41.1pg/ml) or control (167.8 ± 29.6 pg/ml) patients.Serum VEGF also correlated significantly with diseaseactivity, being elevated in patients withmoderate/severe Crohn's disease and ulcerative colitis. Weconclude that serum VEGF is released by inflamed tissuesin children with Crohn's disease. This multifunctionalcytokine could promote inflammation by increasing vascular permeability or promote wound healingby mediating capillary growth.     

Impaired Detoxication of Hydrogen Sulfide in Ulcerative Colitis?

Impaired butyrate oxidation and raised counts of sulfate-reducing bacteria in the colon of patients with ulcerative colitis (UC) indicate that the disease may be induced or aggravated by hydrogen sulfide toxicity. We aimed to examine enzymatic removal of H₂S in erythrocytes and colonic mucosa from controls and patients with UC and Crohn's disease (CD). Rhodanese (RHOD) and thiol methyltransferase (TMT) activities were measured in rectal mucosa and erythrocytes, and plasma thiocyanate was determined. Four groups were analyzed: patients with UC, patients with CD, hospital controls (patients with dyspepsia or IBS), and a group of healthy volunteers. RHOD and TMT activity in rectal biopsies did not differ significantly between controls and patients with UC or CD (n=56). Control levels of RHOD were significantly higher in men than in women (212±25 and 132±14 nmol/mg/min, respectively; P<0.01). In erythrocytes (n=128) RHOD activity was significantly higher in UC patients than in hospital or volunteer controls (1.15±0.12 compared with 0.88±0.12 and 0.66±0.02 nmol/mg/min; P<0.05 and P<0.02, respectively). TMT activity was also significantly higher in erythrocytes from UC patients and hospital controls than volunteer controls (2.02±0.13 pmol/mg/min [P<0.001], 1.51±0.21 pmol/mg/min [P<0.05], and 1.17±0.18 pmol/mg/min, respectively). We found no evidence of defective enzymic detoxication of sulfide by RHOD or TMT in patients with UC or CD.     

Deficiency of Invariant NK T Cells in Crohn's Disease and Ulcerative Colitis

The aim of this study was to investigate whether immunoregulatory invariant NK T cells are deficient in Crohn's disease or ulcerative colitis. Blood was collected for flow cytometry from 106 Crohn's disease, 91 ulcerative colitis, and 155 control subjects. Invariant NK T cells were assessed by Vα24 and (α-galactosylceramide/CD1d tetramer markers. Intracellular cytokine was measured after in vitro anti-CD3 antibody stimulation. Vα24+ T cells were quantified in ileocolonic biopsies as mRNA by real-time PCR and by immunofluorescence. Circulating invariant NK T cells were 5.3% of the control levels in Crohn's (P < 0.001) and 7.9% of the control levels in ulcerative colitis (P < 0.001). Interleukin-4 production was impaired in Crohn's disease and ulcerative colitis. Intestinal Vα24 mRNA expression was 7% in Crohn's disease (P < 0.05) and 9% in ulcerative colitis (P < 0.05). Intestinal Vα24+ T cells were 23% in Crohn's disease but not reduced in ulcerative colitis. We conclude that invariant NK T cells are deficient in Crohn's disease and in ulcerative colitis.