Mucosal changes in inflammatory bowel disease (IBD) are characterized by ulcerative lesions accompanied by prominent cellular infiltrates in the bowel wall. Chemokines are chemotactic cytokines that are able to promote leukocyte migration to areas of inflammation and are also able to initiate cell activation events. They have recently been implicated in the pathophysiology of many disease states. The aim of this study was to detail the degree and distribution of specific chemokines, interleukin (IL)-8, monocyte chemoattractant protein (MCP)-1, -2, and -3, and macrophage inflammatory protein (MIP)-1alpha and -1beta, in IBD mucosa. Thirty-nine patients were included, ten controls, 20 ulcerative colitis (UC), and nine Crohn's disease (CD), with a range of disease activity. Colonic mucosal biopsies were collected from UC, CD, and control patients and embedded in glycol methacrylate. Two-micrometre-thick sections were cut and stained using immunohistochemistry for chemokine protein expression. Sections were analysed using a light microscope. Expression of all types of chemokine protein was detected in colonic mucosa from both control and IBD patients. Patterns of staining between IBD patients and controls differed significantly, but CD and UC patients demonstrated similar patterns of staining. Individual chemokine expression was found to be significantly up-regulated in IBD when patients were compared with the non-diseased group in all areas of the mucosal sections. Up-regulated chemokine expression correlated with increasing activity of the disease. It is concluded that human colonic chemokine expression is non-selectively up-regulated in IBD. The results supported the hypothesis that the degree of local inflammation and tissue damage in UC and CD is dependent on local expression of specific chemokines within IBD tissues.

No abstract

There is increasing evidence to suggest that the potent neutrophil chemoattractant interleukin-8 (IL-8) has an important role in the pathogenesis of inflammatory bowel disease. IL-8 mediates its actions via two cell surface receptors, CXCR1 and CXCR2. This paper describes the distribution of these IL-8 receptors in the normal gastrointestinal tract and how this is modified in ulcerative colitis (UC). Paraffin-embedded colonic resection specimens were stained with monoclonal antibodies directed against CXCR1 and CXCR2 in ten cases of total UC, 16 cases of appendicitis, and 11 histologically normal sections. A semiquantitative scale of 0-4 was used to assess the proportion and intensity of positively stained cells within certain defined areas of tissue. A comparative assessment was made of the distribution of various cell populations. Dual immunostaining was used to confirm the phenotype of positively staining cells. In the histologically normal colon, the antibody against CXCR1 stained a subpopulation of macrophages deep to the epithelium and germinal centre lymphocytes. A similar pattern of staining was seen in acute appendicitis, with in addition some positively stained neutrophil polymorphs. In UC, there was up-regulation of CXCR1, with a striking increase in positively stained macrophages throughout the mucosa and of B and T lymphocytes outside the germinal centre areas. There was also intense up-regulation of CXCR1 expression by the luminal epithelium, reflected in the epithelial staining score (mean+/-SE=1.8+/-0.44 for UC cases, vs. 0.23+/-0.16 for controls and 0.25+/-0.14 for acute appendicitis). CXCR2 was only expressed on a small population of lamina propria mononuclear cells and crypt epithelial cells, with no significant differences observed between the groups. These results suggest that IL-8 may, through CXCR1, have a role beyond neutrophil recruitment in mediating the immune response in UC and that this is not merely a consequence of the acute inflammation seen in UC.

IntroductionSeveral studies have highlighted the risks in patients with a flare of colitis and concomitant Clostridium difficile infection: including increased mortality and increased rates of colectomy in patients with ulcerative colitis (UC). Infection control policies, including antibiotic prescribing, have had an impact on rates of Clostridium difficile associated diarrhoea (CDAD) in the general in-patient population but rates of CDAD in inflammatory bowel disease (IBD) have been reported to be as high as 20%. This study was conducted to investigate the current rates of CDAD in IBD in our Trust.MethodsFor January 2007–2009, case notes for patients with a joint diagnosis of CDAD and IBD (UC and all Crohn's disease (CD)), and hospital audit database for patients with IBD alone, were examined for length of stay, outcomes and medication. Patients were identified by the in-hospital reporting system (Infection Control), as well as discharge diagnoses (Coding). CDAD was diagnosed by positive A/B toxin in standard stool sample testing.ResultsA total of 217 patients with IBD (86 UC) were identified for analysis. 20 patients (12 UC) had CDAD on a pre-existing diagnosis of IBD. This was associated with a dramatically increased average length of stay (38 vs 5.6 days, p<0.001), but not with rates of colectomy (1/12 with UC plus CDAD vs 21/74 with UC alone, p=0.28). Patients with CDAD were older (55.5±20.4 vs 26.8±16.8 years, p<0.05), and 12/20 had received antibiotics for either IBD-related or other pathology, but only 6/20 were on concomitant PPI therapy. Mortality in the CDAD plus UC group was high (2/12), but the deaths occurred in one patient with rectal cancer and another with concomitant chest sepsis. All patients with CDAD received initial therapy with oral or IV metronidazole (in line with Trust practice), and changed to oral vancomycin if diarrhoea had not settled after 10 days (after discussion with the Microbiologist) or if clinical deterioration before this. The use of vancomycin was associated with a longer mean in-patient stay (49.6 vs 28.3 days, p<0.001).ConclusionOur rates for CDAD compare favourably with other case series, but do indicate an increased length of in-patient stay for such patients. Neither increased mortality directly attributable to CDAD, nor increased colectomy rates were detected and may reflect early diagnosis and treatment of CDAD in this “at-risk” patient group. Older patients and those receiving antibiotic therapy for other diagnoses remain the highest risk groups identified.