Levels of tissue factor pathway inhibitor in patients with inflammatory bowel disease

Endothelial dysfunction has been reported to be involved in the pathogenesis of inflammatory bowel disease (IBD) and concomitant thromboembolic complications. Inflammation stimulates the expression of tissue factor and tissue factor pathway inhibitor (TFPI) by endothelial cells. This study assessed the relationship between TFPI levels and disease activity in patients with IBD. A total of 50 consecutive adult patients with ulcerative colitis (UC), 50 patients with Crohn disease (CD), and 50 healthy controls were enrolled to the study. Plasma levels of total TFPI, free TFPI, and von Willebrand factor were measured. Associations among these levels, disease activity, and inflammatory marker levels were assessed. Total TFPI levels were higher in patients with IBD (median, 68.5 [IQR, 60.2-80.1] ng/ml) than in controls (median, 61.1 ng/ml [IQR, 54.3-74.2]; P = 0.01). Free TFPI levels were higher in patients with active UC (median, 12.8 ng/ml [IQR, 11.1-15.4]), inactive UC (median, 9.9 ng/ml [IQR, 7.3-11.5]), active CD (median, 11.7 [IQR, 9.7-14.4] ng/ml), and inactive CD (median,], 9.7 ng/ml [IQR, 8.6-11.6]) than in controls (median, 5.5 ng/ml [IQR, 4.3-7.2]; P <0.001). In the CD and UC groups, free TFPI levels correlated with the levels of inflammatory markers and disease activity. The von Willebrand factor level was higher in patients with UC (median, 143.4 IU/dl [IQR, 115.5–170.4]) and those with CD (median, 151.8 IU/dl [IQR, 112.8-189.4]) than in controls (85.1 IU/dl [IQR, 77.1-101.5]; P <0.001 for both comparisons). The anticoagulant TFPI pathway is activated during remissions and flares in patients with IBD. The free TFPI level correlates with biochemical markers of inflammation and disease activity

Diet and nutritional factors in inflammatory bowel diseases

Inflammatory bowel disease (IBD) development is affected by complex interactions between environmental factors, changes in intestinal flora, various predisposing genetic properties and changes in the immune system. Dietary factors seem to play an underestimated role in the etiopathogenesis and course of the disease. However, research about food and IBD is conflicting. An excessive consumption of sugar, animal fat and linoleic acid is considered a risk factor for IBD development, whereas a high fiber diet and citrus fruit consumption may play a protective role. Also, appropriate nutrition in particular periods of the disease may facilitate achieving or prolonging remissions and most of all, improve the quality of life for patients. During disease exacerbation, a low fiber diet is recommended for most patients. In the remission time, an excessive consumption of alcohol and sulfur products may have a negative effect on the disease course. Attempts are also made at employing diets composed in detail in order to supplement IBD therapy. A diet with a modified carbohydrate composition, a semi-vegetarian diet and a diet low in fermentable oligosaccharides, disaccharides, monosaccharides and polyols are under investigation. Due to chronic inflammation as well as side effects of chronically used medications, patients with IBD are also at increased risk of nutritional factor deficiencies, including iron, calcium, vitamin D, vitamin B12, folic acid, zinc, magnesium and vitamin A. It should also be remembered that there is no single common diet suitable for all IBD patients; each of them is unique and dietary recommendations must be individually developed for each patient, depending on the course of the disease, past surgical procedures and type of pharmacotherapy

Role of interleukins in therapy of inflammatory bowel diseases

Wrzodziejące zapalenie jelita grubego (WZJG) oraz choroba Leśniowskiego-Crohna (ChLC) określane są mianem nieswoistych zapaleń jelit (NZJ). Na ich rozwój wpływ mają złożone interakcje między czynnikami środowiskowymi, predysponującymi cechami genetycznymi, zmianami w zakresie flory jelitowej oraz w systemie immunologicznym. Szczególnie istotną rolę przypisuje się procesom immunologicznym, w które zaangażowane są zarówno mechanizmy komórkowe, jak i humoralne. Terapia biologiczna to leczenie ukierunkowane na różne etapy przebiegu procesu zapalnego. Podstawowe kierunki leczenia obejmują neutralizację cytokin prozapalnych, wykorzystanie cytokin przeciwzapalnych oraz hamowanie adhezji neutrofili. W terapii biologicznej wykorzystuje się przeciwciała przeciw receptorowi IL-2, receptorowi IL-6 czy przeciwciała przeciwko IL-12, IL-17 i IL-23. Podejmuje się również próby podawania interleukin przeciwzapalnych, takich jak rekombinowana IL-10 i IL-11. Obecnie najwięcej uwagi w badaniach klinicznych poświęca się IL-23 i IL-23R, a zahamowanie ich aktywności może być w przyszłości celem terapeutycznym w NZJ. Złożoność terapii biologicznej wymaga dalszych badań klinicznych w celu wykazania, który rodzaj leczenia jest najlepszy w obserwacji długoterminowej.Ulcerative colitis (UC) and Crohn’s disease (CD) are described as inflammatory bowel diseases (IBD). Their development is affected by complex interactions between environmental factors, predisposing genetic factors, changes in intestinal flora and the immune system. A special role is ascribed to immunological processes, which involve both cellular and humoral mechanisms. Biological therapy is focused on different stages of the inflammatory process. It includes pro-inflammatory cytokine neutralization, use of antiinflammatory cytokines, and inhibition of neutrophil adhesion. Antibodies against the IL-2 receptor, IL-6 receptor and against IL-12, IL-17 and IL-23 are used in biological therapy. There are also some trials regarding the use of anti-inflammatory interleukins such as recombinant IL-10 and IL-11. Nowadays many clinical trials are focused on IL-23 and IL-23R. In the future the inhibition of its activity may be a therapeutic goal in IBD. The complexity of biological therapy requires further clinical trials to show which kind of treatment is the best in long-term follow-up

The use of selected neutrophil protein plasma concentrations in the diagnosis of Crohn's disease and ulcerative colitis : a preliminary report

Background: Difficulties in diagnosis of inflammatory bowel disease (IBD) motivate the search for new diagnostic tools, including laboratory tests. The aim of this study was to evaluate concentrations of the neutrophil (NEU) proteins leukocyte elastase (HLE-α1AT), lactoferrin and calprotectin as potential biomarkers used in the diagnosis and assessment of clinical activity of Crohn’s disease (CD) and ulcerative colitis (UC).Material/Methods: The study included 27 patients with CD, 33 patients with UC and 20 healthy controls. Plasma concentrations of calprotectin, lactoferrin and HLE-α1AT were measured using ELISA.Results: In patients with CD higher concentrations of HLE-α1AT (64.3±43.1 vs. 30.1±7.7 ng/l, P&amp;amp;lt;0.001), calprotectin (151.6±97.8 vs. 69.9±22.1 ng/l, P&amp;amp;lt;0.001) and lactoferrin (243.2±102.0 vs. 129.7±32.7 ng/l, P&amp;amp;lt;0.001) than in the control group were found. In patients with UC higher plasma concentrations of HLE-α1AT (62.0±30.9 vs. 30.1±7.7 ng/l, P&amp;amp;lt;0.001), calprotectin (149.6±72.3 vs. 69.9±22.1 ng/l, P&amp;amp;lt;0.001) and lactoferrin (242.6±107.5 vs 129.7±32.7 ng/l, P&amp;amp;lt;0.001) than in the control group were found. HLE-α1AT/NEU and lactoferrin/NEU ratios in patients with UC were significantly higher compared with patients with CD. Calprotectin (P=0.010) and lactoferrin (P=0.023) levels were higher in patients with the active compared with inactive phase of CD.Conclusions: The diagnostic characteristics of plasma granulocyte protein concentrations indicate the usefulness of these tests in the diagnosis of IBD. Higher HLE-α1AT and lactoferrin/NEU ratios in patients with UC than with CD may suggest the usefulness of these ratios in differential diagnostics. Plasma calprotectin and lactoferrin levels may be useful in CD activity assessment

Serum concentration of selected biochemical markers of endothelial dysfunction and inflammation in patients with the varying activity of inflammatory bowel disease

Introduction Endothelial dysfunction leads to an increased expression of cell adhesion molecules, leukocyte diapedesis, vascular smooth‑muscle tone, excessive permeability of vascular walls, and increased procoagulant activity. Objectives We investigated whether serum levels of several endothelial and platelet activation markers correlated with disease activity in patients with inflammatory bowel disease (IBD). Patients and methods This study included 56 patients with ulcerative colitis, 66 with Crohn disease, and 40 healthy controls. We measured the complete blood count and levels of fibrinogen, C‑reactive protein, albumin, interleukin 6, tumor necrosis factor α, E‑selectin, P‑selectin, monocyte chemoattractant protein 1 (MCP‑1), soluble CD40 ligand (sCD40L), and microparticles. Results There were no significant differences in the median levels of E‑selectin, P‑selectin, MCP‑1, sCD40L, and microparticles between patients with active IBD, those with inactive IBD, and healthy controls. The clinical disease activity assessed with the Mayo scale in the ulcerative‑colitis group was weakly, positively correlated with sCD40L (R = 0.32, P = 0.02), P‑selectin (R = 0.32, P = 0.02), and inflammatory marker levels. The clinical disease activity index in the Crohn disease group was positively correlated with the markers of inflammation yet not with the markers of endothelial activity. Conclusions E‑selectin, P‑selectin, sCD40L, MCP‑1, and microparticle levels do not significantly differ between patients with the varying activity of IBD. However, due to the observed correlations, further studies of a larger patient group should be conducted to confirm our observations

Insulin-like growth factor system in remission and flare of inflammatory bowel diseases

Insulin‑like growth factor 1 (IGF‑1) is involved in the modulation of immunity and inflammation. It also plays a role in regulating the migration of endothelial cells and production of vasoactive agents. This study assessed the concentrations of IGF‑1 and insulin‑like growth factor-binding protein 3 (IGFBP‑3) and their relationships to disease activity in patients with inflammatory bowel disease (IBD). A total of 129 adult patients with IBD (69 with Crohn disease [CD] and 60 with ulcerative colitis [UC]) were involved in the study. The control group consisted of 31 healthy volunteers. Biochemical serum analyses were performed and the associations of IGF‑1 and IGFBP‑3 with inflammatory markers and disease activity were assessed. IGF‑1 levels were decreased in patients with active UC compared with those with nonactive UC (mean [SD], 78.3 [22.7] ng/ml and 96.2 [24.5] ng/ml, respectively; P = 0.02) and controls (94.5 [26.5] ng/ml; P = 0.03). The IGF‑1 level was lower in patients with active CD compared with those with nonactive CD (mean [SD], 79.2 [24.9] ng/ml and 110.1 [43.4] ng/ml, respectively; P <0.001). The IGFBP‑3 level was lower in patients with active UC compared with those with nonactive UC (P = 0.04) and controls (P = 0.04). IGF‑1 correlated negatively with C‑reactive protein (CRP) levels (P <0.01), disease activity (P <0.05), and disease duration (P <0.05). IGFBP‑3 levels correlated negatively with CRP levels (P <0.05). The IGF system is disrupted in patients with IBD. Systemic levels of the IGF axis components are related to disease activity and duration