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.     

Increased production of vascular endothelial growth factor by peripheral blood mononuclear cells in patients with inflammatory bowel disease

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic, vascular permeability-enhancing cytokine with overexpression in various pathological disorders, including tumour growth, chronic inflammation and tissue repair. Recent studies have shown significantly increased serum levels of VEGF in patients with inflammatory bowel disease. The origin of the circulating VEGF is still unknown. The present investigation examines the VEGF production by peripheral blood mononuclear cells (PBMCs) in patients with inflammatory bowel disease. METHODS: VEGF levels were measured in culture supernatants of unstimulated PBMCs of 27 patients with inflammatory bowel disease and 10 healthy volunteers using a solid phase ELISA. In addition, VEGF serum levels were determined. RESULTS: PBMCs of both active Crohn's disease patients (1142.6+/-483.9 pg/ml, P < 0.001, n = 12) and active ulcerative colitis patients (748.0+/-637.6 pg/ml, P = 0.006, n = 4) produced significantly higher amounts of VEGF compared with PBMCs of healthy volunteers (113.4+/-101.8 pg/ml, n = 10). In addition, there was a significantly increased VEGF production by PBMCs of patients with active disease compared with PBMCs of patients with quiescent Crohn's disease (261.6+/-254.8 pg/ml, P < 0.001, n = 7) and inactive ulcerative colitis (147.7+/-100.3 pg/ml, P = 0.02, n = 4). There was no significant difference in VEGF release between patients with inactive inflammatory bowel disease and healthy controls. CONCLUSIONS: Significantly increased VEGF production by PBMCs was found in patients with active Crohn's disease and active ulcerative colitis. The study helps to clarify one of the origins of the significantly enhanced VEGF serum levels in patients with active inflammatory bowel disease observed in recent studies.     

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.     

Decreased anti-Saccharomyces cerevisiae antibody titer by mesalazine in patients with Crohn's disease

BACKGROUND: Saccharomyces cerevisiae may contribute to the pathophysiology of Crohn's disease. We determined serum anti-Saccharomyces cerevisiae antibody (ASCA) levels in patients with inflammatory bowel disease. METHODS AND RESULTS: Immunoglobulin G (IgG) ASCA was measured by using an ELISA in serum samples from 19 patients with ulcerative colitis, 18 patients with Crohn's disease and 7 healthy controls. The ASCA level was significantly higher in patients with ulcerative colitis and patients with Crohn's disease than in controls, and was significantly higher in patients with Crohn's disease compared with patients with ulcerative colitis. Age, gender, disease activity, extent of disease and small bowel involvement each did not affect ASCA levels. The use of elemental or polymeric diet therapy for Crohn's disease and administration of corticosteroids to patients with inflammatory bowel disease also did not affect ASCA levels. The ASCA titer was significantly lower in patients with Crohn's disease taking mesalazine than in those not taking it, although, serum IgG levels did not differ between these two groups, which might imply a suppression of IgG production by mesalazine at the intestinal level. CONCLUSIONS: The finding of increased serum ASCA titers in patients with inflammatory bowel disease suggests that Saccharomyces cerevisiae may play a role in the pathophysiology of this condition.     

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.     

Increased production of vascular endothelial growth factor by intestinal mucosa of patients with inflammatory bowel disease.

BACKGROUND/AIMS: Vascular endothelial growth factor (VEGF) is a heparin-binding glycoprotein with potent angiogenic, mitogenic and vascular permeability-enhancing activities specific for endothelial cells. Recent studies have shown significantly increased VEGF serum levels in patients with active Crohn's disease and ulcerative colitis. The origin of the circulating VEGF is not yet completely described. The present investigation examines the VEGF production of colonic mucosa in consideration of mucosal disease activity in patients with inflammatory bowel disease. METHODOLOGY: Fifteen patients with inflammatory bowel disease were studied, 9 patients with Crohn's disease and 6 patients with ulcerative colitis. Biopsies were taken from endoscopically inflamed and non-inflamed colonic mucosa. Therefore, an analysis of the spontaneous VEGF production of cultured biopsies without stimulus and of the histological grade of inflammation scored on a scale of 0-3 (normal mucosa--severe chronic colitis) were performed. Eight patients with irritable bowel syndrome served as controls. VEGF levels in the supernatant of cultured mucosal biopsies were measured using an enzyme linked immunosorbent assay. RESULTS: VEGF production is expressed as pg/mg wet weight of the biopsies. Inflamed mucosa of patients with active ulcerative colitis (16.27 +/- 10.39, p = 0.003, n = 6) and active Crohn's disease (9.88 +/- 5.98, p < 0.012, n = 9) showed a significantly higher spontaneous production of VEGF by colonic mucosa than normal mucosa of controls (3.16 +/- 1.63, n = 8). In addition, there was an increased unstimulated VEGF production by cultured inflamed mucosa of patients with Crohn's disease compared with non-inflamed mucosa (3.88 +/- 3.66, p < 0.015, n = 9). In both Crohn's disease and ulcerative colitis, there was no significant difference between VEGF production by non-inflamed mucosa and normal mucosa of controls. CONCLUSIONS: The present study identifies the intestinal mucosa as one of the origins of the elevated VEGF serum levels in patients with active inflammatory bowel disease and verifies the findings of recent studies about the importance of VEGF in Crohn's disease and ulcerative colitis.     

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)     

T-cell activation in Crohn's disease. Increased levels of soluble interleukin-2 receptor in serum and in supernatants of stimulated peripheral blood mononuclear cells

Serum levels of soluble interleukin-2 receptor were determined in 29 patients with active and quiescent Crohn's disease. In addition, the ability of peripheral blood mononuclear cells of 23 of these patients to generate soluble interleukin-2 receptor following mitogenic stimulation was studied in vitro. Serum soluble interleukin-2 receptor concentrations of patients with active Crohn's disease (n = 19) were significantly elevated (757 +/- 438 U/ml) compared with levels in patients with inactive disease (n = 10; 412 +/- 120 U/ml) and healthy control individuals (n = 40; 375 +/- 102 U/ml; p less than 0.003 and p less than 0.0005, respectively). Serial determinations of serum soluble interleukin-2 receptor concentration in a follow-up of 11 hospitalized patients treated for highly active disease showed a decrease from 1252 +/- 494 U/ml to 527 +/- 193 U/ml (p less than 0.004) that corresponded to clinical improvement, as assessed by Crohn's disease activity index and a reduction of inflammatory parameters. In vitro phytohemagglutinin stimulation of peripheral blood mononuclear cells derived from patients with Crohn's disease resulted in elevated soluble interleukin-2 receptor production not only in patients with active disease (3987 +/- 2439 U/ml), but also in patients with inactive disease (3297 +/- 2282 U/ml), compared with the amount of soluble interleukin-2 receptor produced by mononuclear cells of healthy individuals (1523 +/- 1152 U/ml; p less than 0.005 and p less than 0.02, respectively). In addition, cultivation of mononuclear cells without mitogen resulted in higher soluble interleukin-2 receptor production in patients with active disease than in patients with inactive disease (p less than 0.02). However, patients suffering from active ulcerative colitis also had significantly increased serum levels of soluble interleukin-2 receptor (1080 +/- 400 U/ml) compared with the levels in patients with chronic disease (455 +/- 140 U/ml; p less than 0.0025). In addition, peripheral blood mononuclear cells derived from patients with ulcerative colitis produced significantly more soluble interleukin-2 receptor upon mitogenic stimulation with phytohemagglutinin (2314 +/- 936 U/ml), than cells from healthy controls (1523 +/- 1152 U/ml; p less than 0.05). The finding of elevated soluble interleukin-2 receptor serum levels in patients with active Crohn's disease and its increased production by mononuclear cells of patients with both active and inactive disease is a further example of an alteration of the immune system in this condition; however, this alteration can also be found in other inflammatory bowel diseases.     

Serum tenascin-C is an indicator of inflammatory bowel disease activity

Tenascin-C is a multifunctional matrix protein that is induced in inflammation and neoplasia. In the colonic mucosa of ulcerative colitis patients tenascin-C indicates tissue repair, and mucosal concentrations are correlated with local disease activity. We prospectively examined the relationship between serum concentrations of tenascin-C parameters of disease activity in surgically treated patients with ulcerative colitis and patients with inflammatory bowel disease (IBD). Perioperative serum concentrations were quantified by ELISA in 58 patients admitted for restorative proctocolectomy; controls were 37 patients with familial adenomatous polyposis receiving the same treatment. We also measured tenascin-C serum levels in 47 patients with ulcerative colitis and Crohn's disease who were receiving nonsurgical treatment. Preoperative serum tenascin-C levels were significantly higher in ulcerative colitis patients than in controls (17.2 +/- 14.6 microg/ml vs. 3.2 +/- 1.7 microg/ml) and were significantly correlated with clinical and histological parameters of disease activity; levels decreased significantly after restorative proctocolectomy. Serum tenascin-C levels were also correlated with the course of disease activity in conservatively treated IBD patients. Tenascin-C is thus not disease-specific. However, it does indicate the activity of IBD and may reflect the degree of tissue remodeling. The tenascin-C levels therefore offers a novel serum parameter for assessing disease activity and monitoring therapy in patients with IBD.     

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.     

Increased levels of lipoprotein (a) in Crohn's disease: a relation to thrombosis?

OBJECTIVE: Lipoprotein (a) is recognized as a risk factor for arterial and venous thrombosis, a property that might be related to its structural similarity to plasminogen. Since patients with inflammatory bowel disease frequently suffer from thromboembolic events, we studied the role of lipoprotein (a) in conjunction with lipids and apolipoproteins in Greek patients with ulcerative colitis and Crohn's disease. METHODS: Lipoprotein (a), total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, apolipoprotein A-1 and apolipoprotein B-100 were determined in sera from 129 consecutive fasting Greek patients with inflammatory bowel disease (66 with ulcerative colitis and 63 with Crohn's disease) and from 66 matched healthy controls. RESULTS: In Crohn's disease patients, the mean serum lipoprotein (a) level was significantly higher than in control patients (41.2 mg/dl vs 22.9 mg/dl; P = 0.005). Mean apolipoprotein A-1 and apolipoprotein B-100 levels were significantly lower in Crohn's disease patients than in the controls. In ulcerative colitis patients the mean levels of lipoprotein (a) and apolipoprotein A-1 were not significantly different to the controls, but the levels of apolipoprotein B-100 were significantly lower. Raised levels of lipoprotein (a) of > 30 mg/dl were found in 29 Crohn's disease patients (46%), 15 ulcerative colitis patients (23%) and 11 control patients (17%). Patients with active Crohn's disease had significantly higher mean lipoprotein (a) and lower apolipoprotein A-1 than patients with non-active disease. CONCLUSIONS: Our results suggest that Crohn's disease patients have different lipoprotein (a) and apolipoprotein patterns compared to ulcerative colitis patients and healthy controls. These changes in Crohn's disease patients may possibly expose them to a higher risk of thrombosis.     

Serum and faecal lysozyme in inflammatory bowel disease.

Lysozyme (EC 3.2.1.17) concentrations were measured in the serum and stools of patients with inflammatory bowel disease and compared with the concentrations in similar material from normal controls, patints with non-inflammatory gastrointestinal disease, and patients without gastrointestinal disease. By the turbidometric method, values of lysozyme (microgram/ml +/- SD) are considerably greater in the serum of patients with active Crohn's disease (9.2 +/- 2.7) than in the serum of healthy controls (4.4 +/- 2.0). They do not, however, distinguish individual patients with Crohn's disease from those with ulcerative colitis nor from those with a variety of other gastrointestinal conditions. The lysoplate method gives much higher values for serum lysozyme than the turbidometric method but there is a considerable overlap between the results for patients with Crohn's disease (60.1 +/- 30.7) and normal controls (27.4 +/- 17.5). There is only a moderate correlation between the results given by the two methods (r = 0.56) and it is suggested that factors other than enzyme activity and methodological variation are responsible for the observed differences. This is supported by the finding that, with Crohn's disease in remission, serum lysozyme values (lysoplate) return to normal values but with the turbidometric method remain raised. Mean faecal lysozyme levels, expressed either as a concentration or as total daily excretion, in patients with inflammatory bowel disease are very significantly greater than values in healthy controls and in diseased subjects without diarrhoea but are not significantly different from those subjects with other causes of diarrhoea.     

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.     

Serum Angiogenin in Inflammatory Bowel Disease

Angiogenesis-promoting cytokines have been suggested to play an important role in inflammatory bowel disease (IBD) since they promote inflammation by increasing vascular permeability and mediate tissue repair by activating fibroblasts. The aim of the present study was to evaluate the serum levels of angiogenin, a potent angiogenic factor, in patients with ulcerative colitis (UC) and Crohn's disease (CD). Angiogenin serum levels were measured in 154 IBD patients (78 UC and 76 CD), in 18 cases with other causes of intestinal inflammation, and in 84 matched healthy controls using a commercially available enzyme-linked immunosorbent assay. Angiogenin levels were assessed in terms of disease activity, type, localization, and treatment. Mean (+/-SD) serum angiogenin levels were 526.5+/-224.1 ng/ml in UC patients, 508.8+/-228.5 ng/ml in CD patients, 394.6+/-137.6 ng/ml in healthy controls, and 448.1+/-167.8 ng/ml in patients with non-IBD intestinal inflammation. A statistically significant difference among the mean levels of angiogenin in the four groups was found (P = 0.0003). IBD patients with early disease had a significantly lower mean serum angiogenin compared with patients with late disease (P = 0.03). No significant association between angiogenin levels and disease activity, localization, disease type, or treatment was found. Serum angiogenin is elevated in patients with IBD. The increased serum angiogenin suggests that angiogenin may mediate angiogenesis and vascular permeability in the mucosa of patients with IBD.     

活动性炎症性肠病患者蛋白质和脂代谢的变化

目的 比较炎症性肠病患者及正常对照者之间蛋白质和脂代谢的差异,研究这些差异与疾病活动性及病变部位的关系.方法 回顾性研究1995至2007年溃疡性结肠炎(UC)195例、克罗恩病(CD)76例及正常对照者97名的蛋白质和脂代谢资料.同时评价临床疾病活动指数,红细胞沉降率(ESR)和C-反应蛋白(CRP)水平.性别分层分析蛋白质和脂代谢指标的改变,同时分析蛋白质和脂代谢的改变与疾病活动性及病变部位的关系.结果 UC患者的ESR与血清白球比呈负线性相关(β=-0.521,P＜0.01),与α2-球蛋白呈正线性相关(β=0.319,P＜0.01);CD患者血清球蛋白与ESR(β=0.558,P＜0.01)以及cRP(β=0.424,=P0.01)呈正线性相关.UC患者间因病变部位不同,血清白球比、白蛋白和总胆固醇水平存在显著差异,其中直乙结肠炎患者该三项显著高予其他类型的UC患者(P值分别=0.003、0.005、0.038).CD患者间亦因病变部位不同,血清球蛋白水平存在显著差异,仅累及结肠者的血清球蛋白水平显著高于单纯小肠受累者(P=0.029).结论 UC患者血清白球比和α2-球蛋白的异常程度可作为炎症活动性的预测因素;CD患者血清球蛋白增高预示疾病严重程度活动性增加,累及小肠的CD患者相对仅累及结肠的CD患者而言存在更为严重的营养缺失.     

Mean platelet volume: a useful marker of inflammatory bowel disease activity

OBJECTIVES: We investigated whether the mean platelet volume would be a useful marker in the evaluation of inflammatory bowel disease activity. METHODS: Complete blood count, C-reactive protein, erythrocyte sedimentation rate, serum thrombopoietin and erythropoietin, plasma beta-thromboglobulin, and platelet factor 4 were measured in 93 patients with ulcerative colitis, 66 patients with Crohn's disease, and 38 healthy blood donors. Disease activity was assessed by the Clinical Colitis Activity Index in patients with ulcerative colitis and by the Crohn's Disease Activity Index in patients with Crohn's disease. RESULTS: Mean platelet count was increased in patients with active compared to inactive ulcerative colitis (p < 0.05), and in patients with active compared to inactive Crohn's disease (p = 0.0002) or healthy controls (p < 0.0001). On the other hand, mean platelet volume was significantly decreased in patients with active compared to inactive ulcerative colitis (p = 0.02) or healthy controls (p < 0.0001), and in patients with active compared to inactive Crohn's disease (p = 0.0005) or healthy controls (p < 0.0001). Mean platelet volume was inversely correlated with the white blood cell count (r = -0.17, p = 0.02), C-reactive protein (r = -0.46, p = 0.009) and erythrocyte sedimentation rate (r = -0.28, p = 0.008). No significant correlations were found between mean platelet volume and serum thrombopoietin or erythropoietin levels; however, a strong negative correlation between mean platelet volume and beta-thromboglobulin (r = -0.34, p < 0.0001) and platelet factor 4 (r = -0.30, p = 0.0002) was observed. CONCLUSIONS: Mean platelet volume is significantly reduced in active inflammatory bowel disease and is negatively correlated with the known inflammatory bowel disease activity markers and the platelet activation products. We propose that mean platelet volume provides a useful marker of activity in inflammatory bowel disease.     

Reduced serum insulin-like growth factor-1 (IGF-1) and IGF-binding protein-3 levels in adults with inflammatory bowel disease

In the present study, the changes in circulating IGF-1 and its binding protein IGFBP-3 were determined in adult patients with active inflammatory bowel disease (IBD) in order to assess the effect of this inflammatory condition on the IGF system. IGF-1 and IGFBP-3, as well as interleukin-6 (IL-6) were measured in serum obtained from 22 consecutive newly diagnosed patients (mean age 41.3 years) with active IBD, including 10 patients with Crohn's disease (CD), and 12 with ulcerative colitis (UC). For comparison the same parameters were determined in 30 healthy volunteers matched for age, sex and Body Mass Index (BMI). Serum IGF-1 and IGFBP-3 levels were similar in the two subgroups of patients and the values from all patients were combined for comparison with those from the control group. The mean (+/- SD) serum IGF-1 concentration (178 +/- 91 ng/ml) in the patients with IBD was lower compared with that in the controls (227 +/- 79 ng/ml, P<0.035). Similarly, the mean IGFBP-3 concentration in the patients was lower than in the controls (1.6 +/- 0.6 ng/ml vs 3.2 +/- 0.7 ng/ml respectively, P<0.001), Serum IL-6 levels were higher in the patients compared with the controls (5.5 +/- 4.2 vs 0.65 +/- 0.11 pg/ml, P<0.0001). The reduced IGF-1 and IGFBP-3 levels in patients with active IBD suggest that this systemic inflammatory condition is associated with a degree of acquired GH resistance, possibly induced by inflammatory cytokines.     

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.     

Colonic glycoproteins in monozygotic twins with inflammatory bowel disease

Colonic glycoprotein composition was evaluated in monozygotic twins with inflammatory bowel disease using ion-exchange chromatography. Fifty-three individuals, 12 pairs and 1 single twin with ulcerative colitis and 14 pairs with Crohn's disease, were evaluated. Seven twin pairs were concordant for the presence of ulcerative colitis or Crohn's disease, whereas twin siblings of 10 ulcerative colitis probands and 9 Crohn's disease probands were not known to have inflammatory bowel disease. Content of one chromatographically defined component of colonic mucin, designated HCM species IV, was reduced in both patients with ulcerative colitis (1040 +/- 300 cpm/10,000 cpm total HCM) and their apparently healthy twins (1340 +/- 540 cpm/10,000 cpm total HCM) compared with control subjects (4030 +/- 1,000 cpm/10,000 cpm total HCM). Composition of mucin in Crohn's disease patients and their nonaffected twins was not significantly different than in controls. These observations suggest that altered profiles of mucin glycoprotein may be present before the onset of ulcerative colitis and may be genetically defined. Conversely, it appears that alterations in glycoproteins only are not sufficient to initiate mucosal inflammation.