Quantitative measurement of cytokine mRNA in inflammatory bowel disease: relation to clinical and endoscopic activity and outcome.
OBJECTIVE
The objective of this study was to quantitatively determine cytokine mRNA expression in inflammatory bowel disease under different clinical conditions including active disease, remission or an impaired response to a glucocorticoid (GC) therapy.


METHODS
Mucosal biopsies were taken from 33 patients with ulcerative colitis (UC), 21 patients with Crohn's disease (CD) and 11 controls. Peripheral blood mononuclear cells (PBMNC) were isolated from 24 CU patients, 18 CD patients and 11 controls. Cytokine-mRNA [interleukin (IL)-1beta, IL-2, IL-4, IL-6, IL-10, interferon gamma (IFN-gamma), tumour necrosis factor alpha (TNF-alpha)] expression was measured by quantitative reverse transcriptase-polymerase chain reaction in biopsies and PBMNC, and correlated to endoscopic findings, clinical activity and outcome after 6 months GC therapy.


RESULTS
IL-1beta, IL-6 and TNF-alpha were the largely dominating cytokines. In contrast to IL-1beta and TNF-alpha-, IL-6 expression was restricted to inflamed mucosa and correlated with the clinical activity and C-reactive protein levels in cases of pancolitis ulcerosa. TNF-alpha was elevated in CD even in endoscopic normal tissue. IL-2 and IFN-gamma were downregulated in PBMNC from CD and UC. No Th1 or Th2 specificity could be detected. Cytokine mRNA levels did not correlate with the response to a GC therapy.


CONCLUSIONS
IL-6 sharply distinguishes between inflamed and non-inflamed mucosa, and is therefore a suitable marker of intestinal inflammation. Its selective expression in the inflammatory site makes it an interesting target for future therapeutic strategies. TNF-alpha overexpression even in remission suggests a key role of this cytokine in CD pathogenesis and is possibly a feature that allows one to differentiate CD from UC.
Raddatz
Dirk
D
Medical Clinic, Department of Gastroenterology and Endocrinology, Georg-August University, Göttingen, Germany.
Bockemühl
Miriam
M
Ramadori
Giuliano
G
D000209:Acute-Phase Proteins / Q000096:biosynthesis / Q000235:genetics; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000378:metabolism; D003093:Colitis, Ulcerative / Q000188:drug therapy / Q000276:immunology; D003106:Colon / Q000276:immunology; D003113:Colonoscopy; D003424:Crohn Disease / Q000188:drug therapy / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000235:genetics; D004351:Drug Resistance; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000188:drug therapy / Q000276:immunology*; D015850:Interleukin-6 / Q000096:biosynthesis / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013601:T-Lymphocytes / Q000276:immunology; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000235:genetics
D000209:Acute-Phase Proteins; D015415:Biomarkers; D016207:Cytokines; D005938:Glucocorticoids; D015850:Interleukin-6; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha