Cytokine/chemokine transcript profiles reflect mucosal inflammation in Crohn’s disease
- 232 Downloads
Background and aims
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).
Patients and 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.
Compared to not-inflamed mucosa the vast majority of active CD tissue samples expressed significantly elevated transcript levels of IL-1β, IL-8, IL-23, MRP-14, MIP2α, and MMP-1. Moreover, increased cytokine transcript levels were detected in both active ulcerative colitis and specific colitis. Importantly, TNF-α, IFN-γ, CD40L, and IL-23 transcripts increased in active CD only. Transcript levels (MRP-14, IL-8, MMP-1, MIP2α) 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 MIP2α, MRP-14, TNF-α, and IL-1β transcripts developed an early relapse (n=5) or chronic activity (n=1) during follow-up.
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.
KeywordsCrohn’s disease Cytokine/chemokine transcript profiles Inflammatory bowel disease Mucosal inflammation
The authors thank the nursing staff of the Endoscopy Department for their help in specimen collection. This work was supported in part by a grant from the German Competence Network “Inflammatory Bowel Disease”, AG “Molekulare Marker.”
- 5.Fuss IJ, Neurath M, Boirivant M, et al (1996) Disparate CD4+ lamina propria (LP) lymphokine secretion profiles in inflammatory bowel disease. Crohn’s disease LP cells manifest increased secretion of IFN-gamma, whereas ulcerative colitis LP cells manifest increased secretion of IL-5. J Immunology 157:1261–1270Google Scholar
- 8.Stallmach A, Schäfer F, Weber S, et al (1998) Increased state of activation of CD4-positive T cells and elevated interferon-g production in pouchitis. Gut 43:499–505Google Scholar
- 12.Baron JH, Connell AM, Lennard-Jones JE (1964) Variation between observers in describing mucosal appearance in proctocolitis. BMJ 1:89–92Google Scholar
- 14.Zeitz M (1997) Pathogenesis of inflammatory bowel disease. Digestion 58 [Suppl1]:59–61Google Scholar
- 16.Modigliani R, Mary JY, Simon JF, et al (1990) Clinical, biological, and endoscopic picture of attacks of Crohn’s disease. Evolution on prednisolone. Gastroenterology 98:811–818Google Scholar