Document Detail


Increased interleukin-8 (IL-8) in rectal dialysate from patients with ulcerative colitis: evidence for a biological role for IL-8 in inflammation of the colon.
MedLine Citation:
PMID:  10086655     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Infiltration of neutrophils and their release of toxic reactive oxygen species (ROS) in the colonic mucosa are associated with tissue damage in ulcerative colitis (UC). This neutrophil migration may be induced by chemoattractants, such as cytokines, in the colonic milieu. One such chemoattractant is interleukin-8 (IL-8), a neutrophil chemokine that is present at high concentrations in inflamed mucosa. However, the functional significance of IL-8 in neutrophil attraction and activation in UC has not been established. We hypothesized that IL-8 in the colonic lumen of patients with UC primes neutrophils, leading to their attraction and activation. METHODS: The colonic milieu was sampled by rectal dialysis. Using a semi-permeable membrane with a molecular weight cut-off of 12 kDa, dialysis solution was placed in the rectum and allowed to equilibrate over a 4-h period with the colonic milieu of controls or of patients with UC. IL-8 concentrations were measured by ELISA. Two functions of healthy neutrophils (PMN) were measured: expression of CD11-b surface adhesion molecules (by flow cytometry), and production of ROS (by both chemiluminescence and cytochrome C reduction assays). Neutrophil functions after exposure to rectal dialysates or n-formyl-methionyl-leucyl-phenylalanine (fMLP) were assessed before and after adding anti-IL-8 antibody or the fMLP blocker BMLP. RESULTS: IL-8 concentrations in dialysates from patients with active UC were significantly higher than in controls and correlated with disease activity. UC dialysates significantly increased ROS production and CD11-b expression by neutrophils and anti-IL-8 antibody partially (50%) inhibited these stimulatory effects of UC dialysates. Preincubation of neutrophils with UC dialysates significantly potentiated the fMLP-induced rise in ROS and anti-IL-8 antibody completely abolished this priming effect. CONCLUSIONS: The colonic milieu, sampled by rectal dialysis, from patients with active UC can both activate and prime neutrophils in vitro. High concentrations of IL-8 in the colonic lumen of UC patients are partially responsible for the activating effects of rectal dialysates, and account for all of its priming effects. These findings provide direct evidence for a role for IL-8 in inflammatory bowel disease.
Authors:
A Keshavarzian; R D Fusunyan; M Jacyno; D Winship; R P MacDermott; I R Sanderson
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The American journal of gastroenterology     Volume:  94     ISSN:  0002-9270     ISO Abbreviation:  Am. J. Gastroenterol.     Publication Date:  1999 Mar 
Date Detail:
Created Date:  1999-04-01     Completed Date:  1999-04-01     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  0421030     Medline TA:  Am J Gastroenterol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  704-12     Citation Subset:  IM    
Affiliation:
Department of Medicine, Loyola University Medical School, Maywood, Illinois, USA.
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MeSH Terms
Descriptor/Qualifier:
Adult
Chemiluminescent Measurements
Colitis, Ulcerative / immunology,  metabolism*,  pathology
Colon / immunology,  metabolism*,  pathology
Dialysis Solutions / chemistry
Flow Cytometry
Humans
Interleukin-8 / metabolism*,  physiology
Macrophage-1 Antigen / analysis
Middle Aged
Neutrophil Activation
Neutrophils / immunology,  metabolism
Reactive Oxygen Species / metabolism
Rectum
Grant Support
ID/Acronym/Agency:
DK 40561/DK/NIDDK NIH HHS; DK 43351/DK/NIDDK NIH HHS; DK 47753/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
0/Dialysis Solutions; 0/Interleukin-8; 0/Macrophage-1 Antigen; 0/Reactive Oxygen Species

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