Neutrophil-elastase in chronic inflammatory bowel disease: a marker of disease activity?

BACKGROUND/AIMS: Neutrophil elastase is a proteinase which exists in granulocytes and plays an important role in the pathogenesis of inflammatory disorders. In inflammatory bowel disease there is a leukocyte infiltration of the bowel mucosa. The purpose of this study was to examine whether plasma elastase represents a reliable laboratory marker for establishing the activity of chronic inflammatory bowel disease. METHODOLOGY: We measured plasma elastase concentrations in 61 patients suffering from either Crohn's disease or ulcerative colitis and compared these data with other clinical and laboratory findings and with elastase concentrations in 40 healthy controls. The sensitivity and specificity of the elastase values in chronic IBD were calculated with the use of concomitant measurements of CRP and ESR. RESULTS: Plasma levels were found to be significantly higher in patients (49 micrograms/l) compared with healthy controls (23 micrograms/l). Patients with active disease had higher plasma levels than patients in remission. In general, the sensitivity of elastase to detect active inflammatory bowel disease was about 60%; the specificity was 65%. For patients in remission, the sensitivity was higher than 80%. However, there was a wide range of overlapping values between chronic inactive patients and those with moderately active disease. CONCLUSIONS: We conclude that plasma elastase is a useful independent marker of disease activity in inflammatory bowel disease. Especially for identifying patients in remission, the measurements of elastase seem to be more suitable than other parameters of inflammation, like CRP or ESR.     

Cytomegalovirus and inflammatory bowel disease: Is there a link?

The objective of this report is to give an overall view of the epidemiological, clinical, diagnostic and therapeutic features of Cytomegalovirus (CMV) infection in inflammatory bowel disease (IBD). A review of published reports on this topic was carried out, with particular attention paid to the selection of patients included in studies and the diagnostic methods employed. CMV is frequently associated with IBD. In some cases, CMV infection is as sociated with a poor outcome but it is not clear which patients are more likely to be affected and in which stage of the disease. The use of anti-viral therapy in IBD is controversial and an empirical study with controls is needed. The natural history of CMV infection related to the development and treatment of IBD has not been clarified but it is important to take it in consideration because of the possibility of viral persistence in the immunocompromised host and viral interaction with the immune system.     

CCR5 expression in inflammatory bowel disease and its correlation with inflammatory cells and β-arrestin2 expression

Objective: To elucidate the correlation of expression of CC chemokine receptor 5 (CCR5) with degrees of inflammatory cells infiltration and expression of β-arrestin2 in biopsic intestinal mucosa of the patients with inflammatory bowel disease (IBD).

Methods: Paraffin sections were derived from 53 patients with active IBD, 26 patients with remissive IBD and 30 healthy people. Immunohistochemical envision two-step method was used to test the expression of CCR5 and β-arrestin2 in biopsic intestinal mucosa. HE and toluidine blue staining were used to detect the pathological cytological analysis and classification in lamina propria of colonic mucosa.

Results: The positive rate, strong positive rate and immunohistochemical score of CCR5 expression in active IBD were significantly higher than that in normal controls and remissive IBD (p?<?.05). CCR5 expression had no obvious correlation with clinical severity, lesion distribution and endoscopic classification of active IBD. Neutrophils, eosinophils and lymphocytes in active IBD were significantly higher than that in normal controls and remissive IBD (p?<?.05), while the lymphocyte grade had a positive correlation with CCR5 expression (p?=?.042, r?=?.286). Mastocytes in active IBD, remissive IBD and normal controls had no obvious difference (p?>?.05). β-arrestin2 expression was significantly lower in active IBD than that in remissive IBD and normal controls, and it had a negative correlation with CCR5 expression (p?=?.01, r?=??.247).

Conclusions: CCR5 is highly expressed in active IBD, and it has positive correlation with lymphocyte grade and negative correlation with expression of β-arrestin2.     

Probiotics and inflammatory bowel disease: is there a scientific rationale?

Most conventional forms of drug therapy suppress or modify the host immunoinflammatory response and neglect the other contributor to disease pathogenesis-the environmental microflora. Probiotics are live microbial food ingredients that alter the enteric microflora and have a beneficial effect on health. The rationale for using probiotics in IBD is mainly based on evidence from human studies and experimental animal models implicating intestinal bacteria in the pathogenesis of these disorders. The relationship between bacteria and intestinal inflammation is complex and does not appear to reflect a simple cause and effect. Similarly, the field of probiotics is complex and in need of rigorous research. Until the indigenous flora are better characterized and mechanisms of probiotic action defined, the promise of probiotics in IBD is unlikely to be fulfilled. Because of strain-specific variability and clinical and therapeutic heterogeneity within Crohn's disease and ulcerative colitis, it cannot be assumed that a given probiotic is equally suitable for all individuals. Although preliminary results of probiotic therapy in animal models and humans with ulcerative colitis and pouchitis have been encouraging, their efficacy in treatment or maintenance of remission of Crohn's disease remains to be clarified. However, the circumstantial evidence for some form of biotherapeutic modification of the enteric flora in Crohn's disease seems compelling. In the future, probiotics may offer a simple adjunct to conventional therapy with the emphasis on diet shifting from one of nutritional replenishment alone to a more functional role.     

Matrix metalloproteinases in inflammatory bowel disease: boon or a bane?

Matrix metalloproteinases (MMPs) are a family of Zn(2+)-dependent extracellular matrix (ECM) degrading endopeptidases that share common functional domains, activation mechanisms, and collectively have the capacity to degrade all types of ECM proteins. In addition to playing a central role in ECM turnover, MMPs proteolytically activate or degrade a variety of nonmatrix substrates including chemokines, cytokines, growth factors, and junctional proteins. Thus, they are increasingly recognized as critical players in inflammatory response. Indeed, accumulating data from several studies indicate that they are the predominant proteases involved in the pathogenesis of inflammatory bowel disease (IBD) via their influence on the function and migration of inflammatory cells, mucosal ulceration, as well as matrix deposition and degradation. Some MMPs are constitutively expressed and play a protective role in IBD through their effect on cellular homeostasis, while others are induced during inflammation-mediated tissue damage. This article focuses on the role of the various MMPs in IBD, discussing their physiologic and pathogenetic role in the context of intestinal defense, mucosal inflammatory response, and immune cell-epithelial interaction.     

Oral Campylobacter species: Initiators of a subgroup of inflammatory bowel disease?

In recent years, a number of studies detected a significantly higher prevalence of Campylobacter species such as Campylobacter concisus (C. concisus) in intestinal biopsies and fecal samples collected from patients with inflammatory bowel disease (IBD) compared to controls. Most of these Campylobacter species are not of zoonotic origin but are human oral Campylobacter species. Bacterial species usually cause diseases in the location where they colonize. However, C. concisus and other oral Campylobacter species are associated with IBD occurring at the lower parts of the gastrointestinal tract, suggesting that these Campylobacter species may have unique virulence factors that are expressed in the lower parts of the gastrointestinal tract.     

Microscopic colitis: Is it a spectrum of inflammatory bowel disease?

Lymphocytic and collagenous colitis are forms of microscopic colitis which typically presents in elderly patients as chronic watery diarrhea. The association between microscopic colitis and inflammatory bowel disease is weak and unclear. Lymphocytic colitis progressing to ulcerative colitis has been previously reported; however there is limited data on ulcerative colitis evolving into microscopic (lymphocytic or collagenous) colitis. We report a series of six patients with documented ulcerative colitis who subsequently were diagnosed with collagenous colitis or lymphocytic colitis suggesting microscopic colitis could be a part of the spectrum of inflammatory bowel disease. The median duration of ulcerative colitis prior to being diagnosed with microscopic colitis was 15 years. We noted complete histological and/or symptomatic remission in three out of six cases while the other three patients reverted back into ulcerative colitis suggesting lymphocytic or collagenous colitis could present as a continuum of ulcerative colitis. The exact molecular mechanism of this histological transformation or the prognostic implications is still unclear. Till then it might be prudent to follow up these patients to assess for the relapse of inflammatory bowel disease as well as for dysplasia surveillance.     

A hypothesis: is diverticulitis a type of inflammatory bowel disease?

It is accepted by epidemiologists that diverticula formation in the colon is related to a deficiency in dietary fiber intake, but the cause of acute diverticulitis remains unknown. A hypothesis is presented that acknowledges from the literature that fiber deficiency is also related to an altered intestinal microecology with a change in the bacterial flora. It is hypothesized that the change in the flora with a decrease in their influence on the immune process permits a low-grade chronic inflammation in the mucosa, which is the first step in developing an acute infection of diverticula or diverticulitis. There is some evidence that the low-grade chronic inflammation is present in subjects with diverticula, which is the forerunner of acute diverticulitis. This hypothesis is strengthened by early reports that anti-inflammatory mucosal agents such as mesalamine and immune process regulators such as probiotics may improve diverticulitis.     

Irritable bowel syndrome and inflammatory bowel disease: infectious gastroenteritis-related disorders?

Infectious gastroenteritis may be one of the important factors in the development of irritable bowel syndrome (IBS), with affected individuals often categorized as having post-infectious IBS (PI-IBS), and is linked to the onset of symptoms in approximately 10–20% of patients diagnosed with IBS. Intestinal mucosal infiltration of T cells and mast cells, and enterochromaffin cell hyperplasia are significant immunological and pathological findings that reveal the pathogenesis of PI-IBS, and results of laboratory studies using animal models of PI-IBS clearly support clinical evidence. Recently, infectious gastroenteritis has also been suggested to be associated with the development of inflammatory bowel disease (IBD), and various studies have suggested that individuals with IBS or IBS-like symptoms may be susceptible to initiation of IBD. However, it is still unclear whether infectious gastroenteritis is directly or indirectly (through PI-IBS) linked to the initiation of IBD. Additional studies are necessary to understand the clinical overlap among infectious gastroenteritis, IBS, and IBD.