Cytokine/chemokine transcript profiles reflect mucosal inflammation in Crohn's disease.
OBJECTIVE
Immunoregulatory properties of cytokines may contribute to pathological immune reactions in inflammatory bowel disease. There is an urgent need for a simple and dependable means for quantitating inflammatory activity in mucosal biopsies and assessing relapse risk particularly in patients with active Crohn's disease (CD).


METHODS
Cytokine and chemokine transcripts were quantified using real-time PCR in mucosal biopsy specimens from 70 patients with active inflammatory bowel disease (CD, n=45; ulcerative colitis n=25) and 16 patients with specific colitis (ischemic colitis, infectious colitis). Controls were 12 patients with noninflammatory conditions. CD patients with steroid-induced remission (n=20) were followed for up to 12 months.


RESULTS
Compared to not-inflamed mucosa the vast majority of active CD tissue samples expressed significantly elevated transcript levels of IL-1beta, IL-8, IL-23, MRP-14, MIP2alpha, and MMP-1. Moreover, increased cytokine transcript levels were detected in both active ulcerative colitis and specific colitis. Importantly, TNF-alpha, IFN-gamma, CD40L, and IL-23 transcripts increased in active CD only. Transcript levels (MRP-14, IL-8, MMP-1, MIP2alpha) were correlated with clinical disease activity (CDAI) and endoscopic scoring indices. Medical treatment induced stable remission in 14 of 20 patients which was paralleled by a reduction in increased transcript levels. All six patients without normalization of MIP2alpha, MRP-14, TNF-alpha, and IL-1beta transcripts developed an early relapse (n=5) or chronic activity (n=1) during follow-up.


CONCLUSIONS
Elevated proinflammatory cytokine transcripts in active CD may underlie disease reactivation and chronicity. Real-time PCR quantification is a simple and objective method for grading inflammation of intestinal mucosa and may be useful in identifying patients who would benefit from anti-inflammatory remission maintenance.
Stallmach
Andreas
A
Department of Gastroenterology, Hepatology and Nutritional Medicine, Catholic Clinics Essen-Nord, 45329 Essen, Germany. a.stallmach@kken.de
Giese
Thomas
T
Schmidt
Carsten
C
Ludwig
Bianca
B
Mueller-Molaian
Ina
I
Meuer
Stefan C
SC
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001379:Azathioprine / Q000494:pharmacology; D016022:Case-Control Studies; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D003424:Crohn Disease / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D011237:Predictive Value of Tests; D011239:Prednisolone / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D012680:Sensitivity and Specificity
D018925:Chemokines; D016207:Cytokines; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D011239:Prednisolone; D001379:Azathioprine