Low ileal interleukin 10 concentrations are predictive of endoscopic recurrence in patients with Crohn's disease

Abstract

Background: Endoscopic recurrence after surgery in Crohn's disease is frequent and unpredictable. Abnormal intestinal production of pro- (interleukin (IL)-1β, tumour necrosis factor α (TNF-α)) and anti- (IL-10) inflammatory cytokines has been associated with severe outcome in experimental models of colitis.

Patients and methods: We evaluated if ileal TNF-α, IL-1β, or IL-10 mRNA levels measured at the time of surgery predict endoscopic recurrence, and if ileal IL-10 levels are associated with particular IL-10 promoter alleles. Ileal biopsies were obtained peroperatively from the healthy neoileum of patients undergoing a right ileocolectomy for Crohn's disease. Mucosal TNF-α, IL-1β, and IL-10 mRNA levels were quantified by competitive polymerase chain reaction. A cut off value was determined using a receiver operating curve. IL-10.G promoter haplotypes were analysed using a polymorphic dinucleotide repeat in the IL-10 promoter region.

Results: Three months after surgery, 53% of patients had endoscopic recurrence while 47% remained free of disease. The risk of endoscopic recurrence correlated with ileal IL-10 mRNA concentrations (r²=0.81). Endoscopic recurrence occurred more frequently in patients classified as low IL-10 producers than in those that were high producers (80% v 40%) (p=0.02). Patients with at least one of the two alleles G7–8 or G10–13 produced, respectively, higher (p=0.006) and lower (p=0.029) ileal IL-10 mRNA. The distribution of IL-10.G microsatellite genotypes was similar in patients with or without endoscopic recurrence.

Conclusion: Low ileal IL-10 mRNA concentration is a good marker of endoscopic recurrence in Crohn's disease but the distribution of IL-10.G haplotypes cannot predict the postoperative evolution of the disease.