Published in:
01-09-2007 | Original Article
Interleukin-18 is increased only in a minority of patients with active Crohn’s disease
Authors:
C. Schmidt, T. Giese, R. Goebel, M. Schilling, T. Marth, A. Ruether, S. Schreiber, S. Zeuzem, S. C. Meuer, A. Stallmach
Published in:
International Journal of Colorectal Disease
|
Issue 9/2007
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Abstract
Background and aims
It has been suggested that Crohn’s Disease (CD) is associated with an elevated T helper 1 response as manifested by increased production of interleukin-18 (IL-18). Local concentrations of neutralizing IL-18 binding proteins (IL-18bp) may counteract biological functions of mature IL-18 in mucosal inflammation. Therefore, we investigated the IL-18/IL-18bp system in a large group of patients with active inflammatory bowel disease (IBD) to identify patients that could respond theoretically to IL-18 neutralizing treatment strategies.
Patient/methods
IL-18 and IL-18bp messenger RNA (mRNA) expression in colonic mucosa from patients with active CD (n = 72), active ulcerative colitis (UC; n = 32), and non-IBD controls (infectious colitis or diverticulitis; n = 19) and normal, non-diseased controls (n = 20) were measured by reverse-transcribed real-time polymerase chain reaction. Mature IL-18 protein and IL-18bp expression in inflamed mucosa were assessed by Western blotting.
Results/findings
Although IL-18 mRNA was increased in some patients with CD, the increase was not statistically significant. Densitometric evaluation of IL-18/α-actin ratio in patients with active CD (n = 20) and patients with UC (n = 10) demonstrated an increased ratio of IL-18 protein in CD when compared to UC (1.04 vs 0.72 [median]). On closer inspections, only 7/20 CD patients had an increased IL-18 protein expression in inflamed areas compared to noninflamed mucosa.
Interpretation/conclusion
IL-18 expression in active CD is heterogeneous, only a minority of patients expresses elevated levels. Further treatment strategies targeting IL-18 expression in active CD should be concentrated on this subgroup of patients.