interleukin-8 and Pouchitis

Recent studies demonstrated that depression was associated with mucosal inflammation in patients with ulcerative colitis (UC). This association had not been studied in patients with UC with ileal pouch-anal anastomosis (IPAA) after restorative proctocolectomy. We hypothesized that depression and mucosal proinflammatory cytokines in UC-patients with pouchitis were associated.. We assessed 18 IPAA-UC-patients with pouchitis and 19 IPAA-UC-patients without pouchitis. Mucosal biopsies were taken from the areas with maximal inflammation in the pouch or from the posterior wall of the pouch if the pouch had a normal endoscopic appearance. Disease activity was assessed by the Pouch Disease Activity Index. The expression of mucosal proinflammatory gene transcripts (interleukin-8 [IL-8] and interleukin-1ß [IL-1b]) was quantified by real-time polymerase chain reaction. Depression was assessed by the Hospital Anxiety and Depression Scale (HADS). Pearson correlations between depression and cytokine transcripts were calculated.. The correlation of HADS depression scores of patients with pouchitis with IL-8 was r=0.51 (p=0.03) and with IL-1ß was r=0.47 (p=0.04). The correlation between the HADS depression scores of patients without pouchitis with IL-8 was r=-0.19; (p=0.21) and with IL-1ß was r=-0.12 (p=0.30).. Depression is associated with mucosal proinflammatory cytokines in patients with pouchitis after restorative proctocolectomy in patients with UC.

Topics: Adult; Colitis, Ulcerative; Cross-Sectional Studies; Depression; Female; Humans; Interleukin-1beta; Interleukin-8; Intestinal Mucosa; Male; Middle Aged; Pilot Projects; Polymerase Chain Reaction; Pouchitis; Proctocolectomy, Restorative; Surveys and Questionnaires

Topics: Colitis, Ulcerative; Depression; Female; Humans; Interleukin-1beta; Interleukin-8; Intestinal Mucosa; Male; Pouchitis

Pouchitis after total rectocolectomy is among the most common complications of patients with ulcerative colitis (UC). However, its frequency is quite rare in patients with familial adenomatous polyposis (FAP). We evaluated the inflammatory and pro-apoptotic activity in endoscopically normal mucosa of the ileal pouch in patients with UC and FAP.. Twenty patients (10 with UC and 10 with FAP) with "J" pouch after total proctocolectomy were studied as were 10 normal controls. Biopsies were obtained from the mucosa of the pouch of UC and FAP patients and from the normal ileum of controls. The expression levels of TNF-alpha, IL-1beta, IL-6, IL-8 and phospho-BAD were determined by immunoblotting. Activated NFkappaB was evaluated by immuno-precipitation and immunoblotting for IkappaB kinase beta.. Patients with UC had higher levels of IL-1beta, IL-6, IL-8 and TNF-alpha than patients with FAP. The level of TNF-alpha was higher in patients with UC than in patients with FAP; both patient groups had TNF-alpha levels higher than controls. Activation of NFkappaB was similar in all three groups. The expression of phospho-BAD was significantly lower in patients with FAP than in patients with UC.. As compared with patients with FAP, patients with UC presented increased levels of some pro-inflammatory cytokines, even in the absence of clinical or endoscopic signs of pouchitis. Patients with FAP presented lower levels of pro-inflammatory proteins and of phospho-BAD. These findings may explain the higher rates of progression to pouchitis in UC patients, which could correlate with mucosal atrophy that occurs in inflamed tissue.

Topics: Adenomatous Polyposis Coli; Adult; Analysis of Variance; Apoptosis Regulatory Proteins; bcl-Associated Death Protein; Colitis, Ulcerative; Colonic Pouches; Cytokines; Female; Humans; Immunoblotting; Interleukin-1; Interleukin-6; Interleukin-8; Male; Middle Aged; NF-kappa B; Pouchitis; Proctocolectomy, Restorative; Tumor Necrosis Factor-alpha

Pouchitis is the major long-term complication after ileal pouch-anal anastomosis (IPAA) in patients operated on for ulcerative colitis. The cause is unknown, but both the history of ulcerative colitis and increased bacterial concentration are important factors. Chemokines are mediators for the recruitment of inflammatory cells to the site of inflammation. This study examined the tissue expression of a panel of specific chemokines and the corresponding recruitment of inflammatory cells in IPAA tissue with and without inflammation and after antibiotic treatment.. Biopsy specimens postoperatively from ulcerative colitis patients with IPAA were obtained by endoscopy. Biopsies were taken from 8 patients with noninflamed IPAA and from 14 patients with an episode of acute pouchitis, before and after antibiotic treatment. Biopsies were stained for CD68, CD3, elastase, eotaxin, IP-10, MCP-1, MCP-3, and IL-8 and analyzed by NIH Image analyzer.. Expression of IL-8, MCP-1, MCP-3, and IP-10 was significantly higher in pouchitis than normal pouch. The expression of MCP-1, MCP-3 and IP-10 were significantly lower after antibiotic treatment.. These data support the importance of chemokines for the leukocyte recruitment in pouch tissue during acute pouchitis.

Topics: Adult; Antineoplastic Agents; Chemokine CCL2; Chemokine CXCL10; Chemokines, CC; Chemokines, CXC; Ciprofloxacin; Colitis, Ulcerative; Drug Therapy, Combination; Female; Humans; Immunohistochemistry; Interleukin-8; Male; Pouchitis; Proctocolectomy, Restorative; Rifamycins; Rifaximin

The cytokines interleukin 1beta and interleukin 8 have previously been shown to be present in mucosal biopsy specimens from inflamed ileoanal pouches. Our aim was to use the method of whole gut lavage fluid to measure cytokine concentrations and relate these to disease activity.. Forty-two patients with ulcerative colitis were recruited (23 males). Their ages ranged from 20 to 73 years (median 39). A questionnaire was completed and whole gut lavage, pouchoscopy, and biopsy were performed.. Both interleukin 1beta and interleukin 8 were present in the whole gut lavage fluid of ileoanal pouches, with concentrations ranging from 4 to 143 pg/ml (median 6.3 pg/ml) for whole gut lavage fluid interleukin 1beta and from 18 to 1000 pg/ml (median 53.7 pg/ml) for whole gut lavage fluid interleukin 8. Whole gut lavage fluid interleukin 1beta and interleukin 8 were simultaneously detectable in 24 patients. These included the five patients with pouchitis, who had higher levels of interleukin 1beta (75 pg/ml vs. 8 pg/ml, P < 0.005) and interleukin 8 (668 pg/ml vs. 106 pg/ml, P < 0.005) compared with the rest of the patients with detectable cytokines (n = 19). The sensitivity of whole gut lavage fluid interleukin 8 (>200 pg/ml) in the diagnosis of pouchitis was 1, and the specificity was 0.86. There was a significant positive correlation of both whole gut lavage fluid interleukin 1beta and interleukin 8 with all the gut protein loss markers (immunoglobulin G, albumin, alpha1-antitrypsin).. Cytokine interleukin 1beta and interleukin 8 concentrations, along with other parameters of inflammation, are raised in pouchitis in the whole gut lavage. The results also suggest a spectrum of severity of "pouchitis," with clinical pouchitis fulfilling Moskowitz criteria at the severe end of the spectrum.

Topics: Adult; Enzyme-Linked Immunosorbent Assay; Female; Humans; Interleukin-1; Interleukin-8; Male; Pouchitis; Sensitivity and Specificity; Therapeutic Irrigation

Mucosal lesions of pouchitis are characterized by a neutrophil infiltrate. Interleukin (IL)-8 is the main mediator involved in neutrophil recruitment and is down-regulated by IL-10.. To look for an imbalance between IL-8 and IL-10 in patients with pouchitis.. 18 patients having an ileoanal pouch for ulcerative colitis were studied. Eleven had pouchitis defined by the pouchitis disease activity index of > or =7 points and 7 had no history of pouchitis. Biopsies taken at the site of inflammation or in the normal mucosa were scored for the histologic lesions, the intensity of neutrophil infiltration, and the presence of crypt abscesses. Mucosal IL-8 and IL-10 mRNA were quantified by competitive polymerase chain reaction.. IL-8, IL-10, and IL-10/IL-8 mRNA were similar in patients with or without pouchitis. IL-8 mRNA levels were significantly higher in patients with a histologic score >2 (p = 0.01) and in patients with crypt abscesses (p = 0.01). IL-10/IL-8 mRNA was significantly lower in patients having a histologic score >2 (p = 0.019), a neutrophil infiltration > or =10% (p = 0.013), and crypt abscesses (p = 0.01).. Histologic lesions of pouchitis are associated with a mucosal imbalance between IL-8 and IL-10. IL-10 could be proposed as a new treatment for pouchitis.

Topics: 6-Cyano-7-nitroquinoxaline-2,3-dione; Adolescent; Adult; Humans; Inflammation; Interleukin-10; Interleukin-8; Intestinal Mucosa; Male; Middle Aged; Polymerase Chain Reaction; Pouchitis; RNA, Messenger