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Cytokine mucosal expression in ulcerative colitis, the relationship between cytokine release and disease activity
Ulcerative colitis (UC) is an inflammatory bowel disease with conflicting evidence from studies on the roles of TNFα, IL-8, TGFβ and other cytokines and characterised by neutrophil infiltration and tissue destruction. To compare cytokine profiles of inflamed and non-inflamed mucosa in patients with...
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Published in: | Journal of Crohn's and colitis 2013-07, Vol.7 (6), p.481-489 |
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container_title | Journal of Crohn's and colitis |
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creator | Pearl, Daniel S. Shah, Krina Whittaker, Mark A. Nitch-Smith, Harriet Brown, James F. Shute, Janis K. Trebble, Timothy M. |
description | Ulcerative colitis (UC) is an inflammatory bowel disease with conflicting evidence from studies on the roles of TNFα, IL-8, TGFβ and other cytokines and characterised by neutrophil infiltration and tissue destruction.
To compare cytokine profiles of inflamed and non-inflamed mucosa in patients with distal UC, and matched controls.
Patients were prospectively recruited, mucosal biopsies at flexible sigmoidoscopy (FS) were taken from UC patients within macroscopically inflamed and non-inflamed proximal mucosa, and from age–sex matched controls undergoing FS. Endoscopic and histological inflammation was graded. Quantitative cytokine analysis for IL-4, TNFα, IL-17A, IL-8, IL-10, TGFβ and IFNγ was carried out on tissue homogenates. Statistical comparison was by Wilcoxon signed rank pair analysis, Mann–Whitney U test and Spearman's correlation.
69 active UC patients (54 paired non-inflamed/inflamed mucosa) and 69 controls were compared. In inflamed mucosa, elevation in IL-8 and reduction in TGFβ was measured compared with non-inflamed mucosa (p |
doi_str_mv | 10.1016/j.crohns.2012.07.022 |
format | article |
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To compare cytokine profiles of inflamed and non-inflamed mucosa in patients with distal UC, and matched controls.
Patients were prospectively recruited, mucosal biopsies at flexible sigmoidoscopy (FS) were taken from UC patients within macroscopically inflamed and non-inflamed proximal mucosa, and from age–sex matched controls undergoing FS. Endoscopic and histological inflammation was graded. Quantitative cytokine analysis for IL-4, TNFα, IL-17A, IL-8, IL-10, TGFβ and IFNγ was carried out on tissue homogenates. Statistical comparison was by Wilcoxon signed rank pair analysis, Mann–Whitney U test and Spearman's correlation.
69 active UC patients (54 paired non-inflamed/inflamed mucosa) and 69 controls were compared. In inflamed mucosa, elevation in IL-8 and reduction in TGFβ was measured compared with non-inflamed mucosa (p<0.001; p<0.02) and control mucosa (p<0.001; p<0.001); IL-8 was positively correlated (rs=0.481, p<0.01) and TGFβ inversely correlated (rs=0.462; p<0.01) with grade of inflammation. TNFα concentration was not significantly different. Comparisons of inflamed with non-inflamed mucosa also demonstrate significant reduction in concentration of IFNγ (p<0.001), IL-4 (p<0.005) and IL-17A (p<0.002).
Our findings suggest that IL-8 is elevated and TGFβ is reduced in distal colitis. Lower concentration of IFNγ, IL-4 and IL-17A were also noted. TNFα levels were unchanged. These findings suggest that the inflammatory response in UC may predominantly involve IL-8 mediated neutrophil infiltration and failure of TGFβ mediated tissue healing.]]></description><identifier>ISSN: 1873-9946</identifier><identifier>EISSN: 1876-4479</identifier><identifier>DOI: 10.1016/j.crohns.2012.07.022</identifier><identifier>PMID: 22974822</identifier><language>eng</language><publisher>England: Elsevier B.V</publisher><subject>Adult ; Biopsy ; Case-Control Studies ; Colitis ; Colitis, Ulcerative - drug therapy ; Colitis, Ulcerative - metabolism ; Cytokines - metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Glucocorticoids - therapeutic use ; Humans ; Interferon-gamma ; Interleukin-8 ; Intestinal Mucosa - metabolism ; Male ; Middle Aged ; Prospective Studies ; Severity of Illness Index ; Transforming growth factor beta ; Tumour necrosis factor-alpha ; Ulcerative</subject><ispartof>Journal of Crohn's and colitis, 2013-07, Vol.7 (6), p.481-489</ispartof><rights>2012 European Crohn's and Colitis Organisation</rights><rights>Copyright © 2012 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-9610386bf636660355e77c05d84f9452cb3ebba704983a59d6e50c8de832549e3</citedby><cites>FETCH-LOGICAL-c474t-9610386bf636660355e77c05d84f9452cb3ebba704983a59d6e50c8de832549e3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22974822$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pearl, Daniel S.</creatorcontrib><creatorcontrib>Shah, Krina</creatorcontrib><creatorcontrib>Whittaker, Mark A.</creatorcontrib><creatorcontrib>Nitch-Smith, Harriet</creatorcontrib><creatorcontrib>Brown, James F.</creatorcontrib><creatorcontrib>Shute, Janis K.</creatorcontrib><creatorcontrib>Trebble, Timothy M.</creatorcontrib><title>Cytokine mucosal expression in ulcerative colitis, the relationship between cytokine release and disease activity</title><title>Journal of Crohn's and colitis</title><addtitle>J Crohns Colitis</addtitle><description><![CDATA[Ulcerative colitis (UC) is an inflammatory bowel disease with conflicting evidence from studies on the roles of TNFα, IL-8, TGFβ and other cytokines and characterised by neutrophil infiltration and tissue destruction.
To compare cytokine profiles of inflamed and non-inflamed mucosa in patients with distal UC, and matched controls.
Patients were prospectively recruited, mucosal biopsies at flexible sigmoidoscopy (FS) were taken from UC patients within macroscopically inflamed and non-inflamed proximal mucosa, and from age–sex matched controls undergoing FS. Endoscopic and histological inflammation was graded. Quantitative cytokine analysis for IL-4, TNFα, IL-17A, IL-8, IL-10, TGFβ and IFNγ was carried out on tissue homogenates. Statistical comparison was by Wilcoxon signed rank pair analysis, Mann–Whitney U test and Spearman's correlation.
69 active UC patients (54 paired non-inflamed/inflamed mucosa) and 69 controls were compared. In inflamed mucosa, elevation in IL-8 and reduction in TGFβ was measured compared with non-inflamed mucosa (p<0.001; p<0.02) and control mucosa (p<0.001; p<0.001); IL-8 was positively correlated (rs=0.481, p<0.01) and TGFβ inversely correlated (rs=0.462; p<0.01) with grade of inflammation. TNFα concentration was not significantly different. Comparisons of inflamed with non-inflamed mucosa also demonstrate significant reduction in concentration of IFNγ (p<0.001), IL-4 (p<0.005) and IL-17A (p<0.002).
Our findings suggest that IL-8 is elevated and TGFβ is reduced in distal colitis. Lower concentration of IFNγ, IL-4 and IL-17A were also noted. TNFα levels were unchanged. These findings suggest that the inflammatory response in UC may predominantly involve IL-8 mediated neutrophil infiltration and failure of TGFβ mediated tissue healing.]]></description><subject>Adult</subject><subject>Biopsy</subject><subject>Case-Control Studies</subject><subject>Colitis</subject><subject>Colitis, Ulcerative - drug therapy</subject><subject>Colitis, Ulcerative - metabolism</subject><subject>Cytokines - metabolism</subject><subject>Enzyme-Linked Immunosorbent Assay</subject><subject>Female</subject><subject>Glucocorticoids - therapeutic use</subject><subject>Humans</subject><subject>Interferon-gamma</subject><subject>Interleukin-8</subject><subject>Intestinal Mucosa - metabolism</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Prospective Studies</subject><subject>Severity of Illness Index</subject><subject>Transforming growth factor beta</subject><subject>Tumour necrosis factor-alpha</subject><subject>Ulcerative</subject><issn>1873-9946</issn><issn>1876-4479</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><recordid>eNp9kMtuFDEQRS1ERELgDxDykgXdcfvtDRIa8ZIisUnWlttdo_HQY09sd8j8PQ6dsGRVpapb96oOQu8G0g9kkFf73ue0i6WnZKA9UT2h9AW6GLSSHefKvPzbs84YLs_R61L2hAgjlH6Fzik1imtKL9Dd5lTTrxABHxafipsxPBwzlBJSxCHiZfaQXQ33gH2aQw3lI647wBnmNk2x7MIRj1B_A0Tsn73aFlwB7OKEp1DW3jeXUE9v0NnWzQXePtVLdPv1y83me3f989uPzefrznPFa2fkQJiW41YyKSVhQoBSnohJ863hgvqRwTg6RbjRzAkzSRDE6wk0o4IbYJfow-p7zOlugVLtIRQP8-wipKXYgXEtCKdSNilfpY1oKRm29pjDweWTHYh9hG33doVtH2FbomyD3c7ePyUs4wGmf0fPdJvg0yqA9ud9gGyLDxA9TCGDr3ZK4f8JfwCr8ZQx</recordid><startdate>20130701</startdate><enddate>20130701</enddate><creator>Pearl, Daniel S.</creator><creator>Shah, Krina</creator><creator>Whittaker, Mark A.</creator><creator>Nitch-Smith, Harriet</creator><creator>Brown, James F.</creator><creator>Shute, Janis K.</creator><creator>Trebble, Timothy M.</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20130701</creationdate><title>Cytokine mucosal expression in ulcerative colitis, the relationship between cytokine release and disease activity</title><author>Pearl, Daniel S. ; Shah, Krina ; Whittaker, Mark A. ; Nitch-Smith, Harriet ; Brown, James F. ; Shute, Janis K. ; Trebble, Timothy M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c474t-9610386bf636660355e77c05d84f9452cb3ebba704983a59d6e50c8de832549e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Adult</topic><topic>Biopsy</topic><topic>Case-Control Studies</topic><topic>Colitis</topic><topic>Colitis, Ulcerative - drug therapy</topic><topic>Colitis, Ulcerative - metabolism</topic><topic>Cytokines - metabolism</topic><topic>Enzyme-Linked Immunosorbent Assay</topic><topic>Female</topic><topic>Glucocorticoids - therapeutic use</topic><topic>Humans</topic><topic>Interferon-gamma</topic><topic>Interleukin-8</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Prospective Studies</topic><topic>Severity of Illness Index</topic><topic>Transforming growth factor beta</topic><topic>Tumour necrosis factor-alpha</topic><topic>Ulcerative</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pearl, Daniel S.</creatorcontrib><creatorcontrib>Shah, Krina</creatorcontrib><creatorcontrib>Whittaker, Mark A.</creatorcontrib><creatorcontrib>Nitch-Smith, Harriet</creatorcontrib><creatorcontrib>Brown, James F.</creatorcontrib><creatorcontrib>Shute, Janis K.</creatorcontrib><creatorcontrib>Trebble, Timothy M.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of Crohn's and colitis</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pearl, Daniel S.</au><au>Shah, Krina</au><au>Whittaker, Mark A.</au><au>Nitch-Smith, Harriet</au><au>Brown, James F.</au><au>Shute, Janis K.</au><au>Trebble, Timothy M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cytokine mucosal expression in ulcerative colitis, the relationship between cytokine release and disease activity</atitle><jtitle>Journal of Crohn's and colitis</jtitle><addtitle>J Crohns Colitis</addtitle><date>2013-07-01</date><risdate>2013</risdate><volume>7</volume><issue>6</issue><spage>481</spage><epage>489</epage><pages>481-489</pages><issn>1873-9946</issn><eissn>1876-4479</eissn><abstract><![CDATA[Ulcerative colitis (UC) is an inflammatory bowel disease with conflicting evidence from studies on the roles of TNFα, IL-8, TGFβ and other cytokines and characterised by neutrophil infiltration and tissue destruction.
To compare cytokine profiles of inflamed and non-inflamed mucosa in patients with distal UC, and matched controls.
Patients were prospectively recruited, mucosal biopsies at flexible sigmoidoscopy (FS) were taken from UC patients within macroscopically inflamed and non-inflamed proximal mucosa, and from age–sex matched controls undergoing FS. Endoscopic and histological inflammation was graded. Quantitative cytokine analysis for IL-4, TNFα, IL-17A, IL-8, IL-10, TGFβ and IFNγ was carried out on tissue homogenates. Statistical comparison was by Wilcoxon signed rank pair analysis, Mann–Whitney U test and Spearman's correlation.
69 active UC patients (54 paired non-inflamed/inflamed mucosa) and 69 controls were compared. In inflamed mucosa, elevation in IL-8 and reduction in TGFβ was measured compared with non-inflamed mucosa (p<0.001; p<0.02) and control mucosa (p<0.001; p<0.001); IL-8 was positively correlated (rs=0.481, p<0.01) and TGFβ inversely correlated (rs=0.462; p<0.01) with grade of inflammation. TNFα concentration was not significantly different. Comparisons of inflamed with non-inflamed mucosa also demonstrate significant reduction in concentration of IFNγ (p<0.001), IL-4 (p<0.005) and IL-17A (p<0.002).
Our findings suggest that IL-8 is elevated and TGFβ is reduced in distal colitis. Lower concentration of IFNγ, IL-4 and IL-17A were also noted. TNFα levels were unchanged. These findings suggest that the inflammatory response in UC may predominantly involve IL-8 mediated neutrophil infiltration and failure of TGFβ mediated tissue healing.]]></abstract><cop>England</cop><pub>Elsevier B.V</pub><pmid>22974822</pmid><doi>10.1016/j.crohns.2012.07.022</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adult Biopsy Case-Control Studies Colitis Colitis, Ulcerative - drug therapy Colitis, Ulcerative - metabolism Cytokines - metabolism Enzyme-Linked Immunosorbent Assay Female Glucocorticoids - therapeutic use Humans Interferon-gamma Interleukin-8 Intestinal Mucosa - metabolism Male Middle Aged Prospective Studies Severity of Illness Index Transforming growth factor beta Tumour necrosis factor-alpha Ulcerative |
title | Cytokine mucosal expression in ulcerative colitis, the relationship between cytokine release and disease activity |
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