Low ileal interleukin 10 concentrations are predictive of endoscopic recurrence in patients with Crohn's disease.
BACKGROUND
Endoscopic recurrence after surgery in Crohn's disease is frequent and unpredictable. Abnormal intestinal production of pro- (interleukin (IL)-1 beta, tumour necrosis factor alpha (TNF-alpha)) and anti- (IL-10) inflammatory cytokines has been associated with severe outcome in experimental models of colitis.


METHODS
We evaluated if ileal TNF-alpha, IL-1 beta, 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-alpha, IL-1 beta, 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 (r(2)=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.


CONCLUSIONS
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.
Meresse
B
B
Equipe Propre Institut National de la Santé et de la Recherche Médical 0114 sur la Physiopathologie des Maladies Inflammatoires Intestinales, CHU Lille, France.
Rutgeerts
P
P
Malchow
H
H
Dubucquoi
S
S
Dessaint
J P
JP
Cohard
M
M
Colombel
J F
JF
Desreumaux
P
P
D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D003424:Crohn Disease / Q000378:metabolism*; D005260:Female; D006239:Haplotypes; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis*; D016753:Interleukin-10 / Q000032:analysis*; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D018895:Microsatellite Repeats; D011237:Predictive Value of Tests; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000032:analysis; D012372:ROC Curve; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
D007375:Interleukin-1; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10