A high serum concentration of interleukin-6 is predictive of relapse in quiescent Crohn's disease.
OBJECTIVE
Relapses of Crohn's disease are difficult to predict. We assessed the value of serum level of interleukin-6, tumour necrosis factor alpha (TNF-alpha) and soluble TNF receptors as predictors of relapse in quiescent Crohn's disease.


METHODS
Thirty-six patients with inactive Crohn's disease, treated or not, were included. Various clinical and biological parameters, including interleukin-6, TNF-alpha and soluble TNF receptors serum levels were measured at inclusion in the study and the patients were followed clinically for 1 year. The relapse was defined as a Crohn's Disease Activity Index (CDAI) greater than 150 with an increase greater than 100 compared to the inclusion value. We analysed the ability of these parameters to predict relapse in parallel to clinical characteristics and other laboratory parameters.


RESULTS
Among the 32 variables tested, interleukin-6 serum level had the greatest ability to predict the time-to-relapse, with 17-fold chance of relapse over a 1-year period for patients with an interleukin-6 serum level greater than 20 pg/ml than for patients with a lower level (P < 0.001). A high serum level of the soluble TNF receptors p55 and p75 also had significant predictive value, in contrast to TNF-alpha serum levels. An interleukin-6 serum level greater than 20 pg/ml and either an acid alpha-1-glycoprotein level greater than 1.1 g/l or a soluble interleukin-2 receptor serum level greater than 95 pM/l were risk factors selected by a stepwise multivariate analysis. In both models a good prognosis group was defined by the absence of the two risk factors, a bad prognostic group by the presence of the two risk factors and an intermediate in between. With both models, the good prognosis group included 17 patients who experienced no relapse over the 1-year follow-up, whereas all patients (seven with the first model and six with the second) in the bad prognosis group had a relapse during the follow-up. Looking specifically at two homogeneous subgroups including either naturally/5-aminosalicylic acid (5-ASA) quiescent or corticoid quiescent patients, a very good predictive value for interleukin-6 serum concentration was also found.


CONCLUSIONS
Interleukin-6 serum level alone or in association with other biological parameters such as acid alpha-1-glycoprotein or the soluble interleukin-2 receptor serum level may be useful for predicting the course of the disease in patients with quiescent Crohn's disease.
Louis
E
E
Department of Gastroenterology, CHU of Liège, Belgium.
Belaiche
J
J
van Kemseke
C
C
Franchimont
D
D
de Groote
D
D
Gueenen
V
V
Mary
J Y
JY
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D003424:Crohn Disease / Q000097:blood / Q000503:physiopathology*; D006801:Humans; D015850:Interleukin-6 / Q000097:blood*; D008875:Middle Aged; D015999:Multivariate Analysis; D009961:Orosomucoid / Q000378:metabolism; D016016:Proportional Hazards Models; D015375:Receptors, Interleukin-2 / Q000097:blood; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood; D012008:Recurrence; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015415:Biomarkers; D015850:Interleukin-6; D009961:Orosomucoid; D015375:Receptors, Interleukin-2; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha