The insulin-like growth factor system and markers of inflammation in adult patients with inflammatory bowel disease

BACKGROUND AND OBJECTIVES: Catabolism and growth impairment are well-known complications of inflammatory bowel disease (IBD). Recent studies have demonstrated significant changes in the IGF system in IBD patients. The aim of the present study was to investigate correlations between the IGF system and markers of inflammation in IBD. METHODS: A cross-sectional study comprising 99 IBD patients (Crohn's disease (CD, n = 50) and ulcerative colitis (UC, n = 49)). Correlations between markers of inflammation and IGF-I, IGF-II and IGFBP-3 were examined in CD and UC patients in remission and relapse. The patients were clinically scored using Crohn's Disease Activity Index (CDAI) for CD patients and Activity Index (AI) for UC patients. RESULTS: In the UC group we found correlations between IGF-I and CRP (r(s) = Spearman's rho) (r(s) = -0.40, p < 0.01) and albumin (r(s) = 0.46, p < 0.001), IGFBP-3 and albumin (r(s) = 0.36, p < 0.01) and AI score (r(s) = -0.31, p < 0.05). IGF-II correlated with CRP (r(s) = -0.42, p < 0.01), IL-6 (r(s) = -0.65, p < 0.001), albumin (r(s) = 0.41, p < 0.01), AI score (r(s) = -0.30, p < 0.05) and orosomucoid (r(s) = -0.47, p < 0.001). In the CD group we found correlations between IGF-I and CRP (r(s) = -0.40, p < 0.05), and albumin (r(s) = -0.46, p < 0.01), IGFBP-3 and albumin (r = 0.36, p < 0.01). IGF-II correlated with IL-6 (r(s) = -0.65, p < 0.001), albumin (r(s) = 0.41, p < 0.01), CDAI score (r(s) = -0.30, p < 0.05) and orosomucoid (r(s) = -0.47, p < 0.001). CONCLUSIONS: IGF-I, IGF-II and IGFBP-3 are correlated to albumin and IGF-I and IGF-II are correlated to CRP in IBD patients. Further, IGF-II is correlated to IL-6 in IBD patients. This may suggest a correlation between inflammation and the IGF system with involvement in muscle and bone catabolism in IBD.     

Molecular-phylogenetic characterization of microbial communities imbalances in the small intestine of dogs with inflammatory bowel disease

An association between luminal commensal bacteria and inflammatory bowel disease (IBD) has been suggested in humans, but studies investigating the intestinal microbial communities of dogs with IBD have not been published. The aim of this study was to characterize differences of the small intestinal microbial communities between dogs with IBD and healthy control dogs. Duodenal brush cytology samples were endoscopically collected from 10 dogs with IBD and nine healthy control dogs. DNA was extracted and 16S rRNA gene was amplified using universal bacterial primers. Constructed 16S rRNA gene clone libraries were compared between groups. From a total of 1240 selected clones, 156 unique 16S rRNA gene sequences were identified, belonging to six phyla: Firmicutes (53.4%), Proteobacteria (28.4%), Bacteroidetes (7.0%), Spirochaetes (5.2%), Fusobacteria (3.4%), Actinobacteria (1.1%), and Incertae sedis (1.5%). Species richness was significantly lower in the IBD group (P=0.038). Principal component analysis indicated that the small intestinal microbial communities of IBD and control dogs are composed of distinct microbial communities. The most profound difference involved enrichment of the IBD dogs with members of the Enterobacteriaceae family. However, differences involving members of other families, such as Clostridiaceae, Bacteroidetes and Spirochaetes, were also identified. In conclusion, canine IBD is associated with altered duodenal microbial communities compared with healthy controls.     

Chemokine and cytokine levels in inflammatory bowel disease patients

Crohn’s disease (CD) and ulcerative colitis (UC), two forms of inflammatory bowel disease (IBD), are chronic, relapsing, and tissue destructive lesions that are accompanied by the uncontrolled activation of effector immune cells in the mucosa. Recent estimates indicate that there are 1.3 million annual cases of IBD in the United States, 50% of which consists of CD and 50% of UC. Chemokines and cytokines play a pivotal role in the regulation of mucosal inflammation by promoting leukocyte migration to sites of inflammation ultimately leading to tissue damage and destruction. In recent years, experimental studies in rodents have led to a better understanding of the role played by these inflammatory mediators in the development and progression of colitis. However, the clinical literature on IBD remains limited. Therefore, the aim of this study was to evaluate systemic concentrations of key chemokines and cytokines in forty-two IBD patients with a range of disease activity compared to levels found in ten healthy donors. We found a significant increase in an array of chemokines including macrophage migration factor (MIF), CCL25, CCL23, CXCL5, CXCL13, CXCL10, CXCL11, MCP1, and CCL21 in IBD patients as compared to normal healthy donors (P < 0.05). Further, we also report increases in the inflammatory cytokines IL-16, IFN-γ, IL-1β and TNF-α in IBD patients when compared to healthy donors (P < 0.05). These data clearly indicate an increase in circulating levels of specific chemokines and cytokines that are known to modulate systemic level through immune cells results in affecting local intestinal inflammation and tissue damage in IBD patients. Blockade of these inflammatory mediators should be explored as a mechanism to alleviate or even reverse symptoms of IBD.     

Multi-omics reveal microbial determinants impacting responses to biologic therapies in inflammatory bowel disease

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Cytokines in inflammatory bowel disease

Over the past decade, much has been learned regarding the role of various cytokines in the pathogenesis of inflammatory bowel disease. Several cytokine 'knockout' models in mice have been shown to develop colitis, while alterations in the production of various cytokines has been documented in human Crohn's disease and ulcerative colitis. In recent years, attempts have been made to treat these diseases through modulation of cytokine production or action. This review focuses on the cytokines that have been implicated in the pathogenesis of inflammatory bowel disease. The evidence for and against a role for particular cytokines in intestinal inflammation is reviewed, as is the experimental and clinical data suggesting that cytokines are rational targets for the development of new therapies.     

Somatostatin in inflammatory bowel disease

Intestinal inflammation is controlled by various immunomodulating cells, interacting by molecular mediators. Neuropeptides, released by enteric nerve cells and neuroendocrine mucosa cells, are able to affect several aspects of the general and intestinal immune system, with both pro- as well as anti-inflammatory activities. In inflammatory bowel disease (IBD) there is both morphological as well as experimental evidence for involvement of neuropeptides in the pathogenesis. Somatostatin is the main inhibitory peptide in inflammatory processes, and its possible role in IBD is discussed.     

The biopsychosocial model of treatment the patients with inflammatory chronic bowel disease

We present the organised psychological group interventions for persons with inflammatory bowel disease (ulcerose colitis, Morbus Crohn). The actual bio-psychosocial model of health and illness is used to explain the situation of chronically ill patient as stressful life position and their ways of coping with such, health-related problems. Considering that numerous psychological factors can lead to insufficient illness adaptation and (non) adherence to treatment--and all those--to much more complications and higher use of therapies, we try to develop for group of those patients effective model of treatment. The group of 15 gastroenterological patients from treatment in UKC Maribor was included in the psycho-diagnostic procedure (semi-structural interview, The Freiburg's Personal Inventory, The Coping Inventory for Stressful Situations, Health-related Questionnaire of Quality of Life). The data that we had been gathered were significant to the C-type of coping, found in some other group of chronically ill patients, too. For such persons is typically their low emotions expressiveness, especially negative emotions (sadness, anger). In interpersonal contacts they usually show extreme social agreement and low level of assertiveness. So we formed our therapeutic model and its therapeutic aims to the course of being able to express the emotions, to reach higher personal autonomy, better assertively and self image--which at the end have all greater influence on the human's quality of life. After therapeutic model and aims of treatment has been formed, patients with inflammatory bowel disease were treated in cognitive-behavioural group, where also C. Roger's conditions for successful psychotherapy were taken in account and were the part of hole, integrative form of treatment.     

益生菌在儿童炎症性肠病中的应用

炎症性肠病（inflammatory bowel disease,IBD）是一种原因不明的慢性非特异性肠道炎性疾病,主要包括溃疡性结肠炎（ulcerative colitis,UC）、克罗恩病（Crohn's disease,CD）和未定型的炎症性肠病（IBD-unclassified,IBDU）。随着对肠道微生物与IBD关系认识的不断加深,许多研究发现肠道菌群的生态失调在IBD的发病中起着重要作用。益生菌在儿童IBD治疗中具有良好前景,但仍缺乏有效的证据来确证益生菌疗效,并指导临床对益生菌的种类和剂量等进行选择。现有研究表明,益生菌对儿童IBD的治疗具有特异性,在诱导和维持UC缓解效果明显,但在诱导CD缓解、维持CD缓解和预防术后并发症及复发方面效果并不理想。     

Methylenetetrahydrofolate reductase C677T variant in Moroccan patients with inflammatory bowel disease

Background

The association of genetic polymorphisms related to metabolism of homocysteine and folate with inflammatory bowel disease has been evidenced. Several studies have identified genetic variants of MTHFR as significant susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC). The C677T genetic polymorphism in the MTHFR gene is found to be associated with a thermolabile variant enzyme that shows a reduced activity. Therefore, we investigated whether the C677T variant confers genetic susceptibility to CD or UC and evaluated the genotype–phenotype associations in the Moroccan population.

Methods

The present study included 96 inflammatory bowel disease patients (68 patients with CD and 28 with UC) and 182 healthy controls. DNA samples were genotyped for the MTHFR (C677T) mutation by the PCR-RFLP method. Statistical analyzes were performed using MedCalc software, Chi square test and Fisher test.

Results

The respective odds ratio for CD, UC and control group were, 1.55 (CI 95%: 0.53–4.53, P = 0.52); 0.50 (CI 95%: 0.06–4.15, P = 0.52) and 0.50 (CI 95%: 0.06–4.15, P = 0.52). Thus, no statistically significant association with the disease was observed in frequency of the TT variant in comparison to healthy controls. Stratification of IBD patients on the basis of CD or UC showed that individuals carrying at least one T allele are not protected against Crohn's disease. Furthermore, clinical features of the disease did not show any significant association.

Conclusion

In conclusion, the present study indicates that the genetic risk for IBD is not modulated by MTHFR C677T polymorphism in Moroccan population.     

New cytokine therapeutics for inflammatory bowel disease

Conventional therapy for inflammatory bowel diseases rely on corticosteroids and 5-aminosalicylates combined with immunosuppressive agents for maintenance. These drugs are not always effective and may inflict serious side effects. Other therapies are therefore awaited. Infliximab, a monoclonal antibody against the pro-inflammatory cytokine TNF-alpha has been successfully applied as a treatment for Crohn's disease. The mechanism of action of this drug extends beyond the level of TNF-alpha scavenging and includes induction of apoptosis of effector cells. Numerous anti-TNF antibodies have been developed and are currently evaluated in clinical trials. Other targets for monoclonal antibodies include integrins and cytokines involved in T-cell differentiation and activation. Likewise recombinant proteins that moderate TNF bioactivity and lymphocyte function have been developed. The therapeutic effect of recombinant interleukin-10 seems to be dependent on local delivery of the protein. Antisense therapy targeting lymphocyte migration has also been tested in IBD. Finally, the conventional drug thalidomide and possibly MAP-kinase inhibitors may become novel treatment entities for IBD.     

Phospholipid transfer protein activity is associated with inflammatory markers in patients with cardiovascular disease

Plasma phospholipid lipid transfer protein (PLTP) has several known key functions in lipoprotein metabolism. Recent studies suggest that it also may play a role in the inflammatory response. Inflammatory cell activity contributes to the development of atherosclerosis. To seek further evidence for the association of PLTP with inflammation, we studied the relationship between PLTP activity and five inflammatory markers [C-reactive protein (CRP), serum amyloid A (SAA), interleukin 6 (IL-6), white blood cells (WBC), and fibrinogen] in 93 patients with low HDL and cardiovascular disease (CVD). Plasma PLTP activity had the strongest correlation with CRP (r=0.332, P<0.001) followed by SAA (r=0.239, P=0.021). PLTP, CRP, and SAA were significantly associated with body mass index (BMI), insulin or glucose, apolipoprotein (apo) B, and/or apo E level (r=0.264-0.393, P<0.01). PLTP, SAA, and IL-6 also were associated with the concentration of HDL particles without apo A-II [Lp(A-I)](r=0.373-0.472, P<0.005, n=56), but not particles with apo A-II. Smoking was associated with increased PLTP activity, CRP, and WBC, and hypertension with increased PLTP activity. In linear models, CRP remained significantly associated with PLTP after adjustment of CVD risk factors and insulin resistance. Also, much of the variability of plasma PLTP activity was explained by CRP, BMI, Lp(A-I), smoking, glucose, and blood pressure. These findings show for the first time that plasma PLTP activity is associated positively with CRP in CVD, a state of chronic inflammation.     

Lipoxin biosynthesis in inflammatory bowel disease

BACKGROUND AND AIMS: Lipoxins are anti-inflammatory lipid mediators that are produced in gut mucosa, which serve to limit and resolve persistent inflammation. The purpose of this study was to evaluate colonic lipoxin biosynthesis in patients with ulcerative colitis (UC) to establish a possible biochemical basis for persistent inflammation in UC. METHODS: Colonic mucosa from patients with UC or organ donors (controls) was placed into tissue culture for 90 min. The conditioned media was assayed (ELISA) for lipoxin A4 (LXA) and the biologically active isomer 15-epi-LXA4 (aspirin triggered lipoxin, ATL). Mucosal tissue 15-lipoxygenase protein was determined by Western blot. RESULTS: Patient colonic mucosa produced significantly lower (12-fold) amounts of LXA, relative to organ donors. This occurred irregardless of patient steroid treatment. However, patient tissue responded to in vitro aspirin by synthesizing biologically active ATL. For the first time, human colonic mucosa was found to synthesize 15-lipoxygenase-2, an epithelial-derived isoenzyme used for lipoxin synthesis. These levels were significantly lower in UC patients compared to the control tissue. Finally, mice chronically treated with a putative selective 15-lipoxygenase inhibitor (PD 146176) experienced significantly worse intestinal function during experimental colitis, relative to untreated mice. CONCLUSION: Colonic mucosa from UC patients demonstrated defective lipoxin biosynthesis, which may contribute to the inability of these patients to resolve persistent colonic inflammation.     

A genomewide analysis provides evidence for novel linkages in inflammatory bowel disease in a large European cohort

Inflammatory bowel disease (IBD) is characterized by a chronic relapsing intestinal inflammation, typically starting in early adulthood. IBD is subdivided into two subtypes, on the basis of clinical and histologic features: Crohn disease and ulcerative colitis (UC). Previous genomewide searches identified regions harboring susceptibility loci on chromosomes 1, 3, 4, 7, 12, and 16. To expand our understanding of the genetic risk profile, we performed a 9-cM genomewide search for susceptibility loci in 268 families containing 353 affected sibling pairs. Previous linkages on chromosomes 12 and 16 were replicated, and the chromosome 4 linkage was extended in this sample. New suggestive evidence for autosomal linkages was observed on chromosomes 1, 6, 10, and 22, with LOD scores of 2.08, 2.07, 2.30, and 1.52, respectively. A maximum LOD score of 1.76 was observed on the X chromosome, for UC, which is consistent with the clinical association of IBD with Ullrich-Turner syndrome. The linkage finding on chromosome 6p is of interest, given the possible contribution of human leukocyte antigen and tumor necrosis-factor genes in IBD. This genomewide linkage scan, done with a large family cohort, has confirmed three previous IBD linkages and has provided evidence for five additional regions that may harbor IBD predisposition genes.     

Design of nanozymes for inflammatory bowel disease therapy

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