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Interleukin-18 and its binding protein in patients with inflammatory bowel disease during remission and exacerbation
Timna Naftali1, Daniella Novick, Gila Gabay
1Institute of Gastroenterology and Liver Diseases, Meir Hospital, Kfar Saba, Israel. naftali@post.tau.ac.il
Background:
Crohn's disease and ulcerative colitis are inflammatory bowel diseases with an unknown etiology. Interleukin-18 is a pro-inflammatory cytokine that is up-regulated in Crohn's disease. IL-18 binding protein neutralizes IL-18. The relationship of IL-18 and IL-18BP and disease activity in these diseases is not fully understood.
Objectives:
To investigate the correlation of IL-18 and IL-18BP with disease activity and other disease parameters in inflammatory bowel disease.
Methods:
IL-18 and IL-18BP isoform a were measured in 129 patients and 10 healthy individuals. Patients' mean age was 40.5 (range 15-70 years) and 43 were women; 58 Crohn's and 28 colitis patients were in remission and 52 and 14, respectively, were in exacerbation. Twenty-three (19 and 4 respectively) were studied in both remission and exacerbation.
Results:
The mean level of free IL-18 was significantly different between healthy individuals and Crohn patients, and between Crohn patients during exacerbation and remission (167 +/- 32 vs. 471 +/- 88 and 325 +/- 24 pg/ml, respectively, P < 0.05). Mean level of IL-18BP was significantly different between healthy individuals and Crohn patients, and between Crohn patients during exacerbation and remission (2.1 +/- 1.1, 7.5 +/- 4 and 5.23 +/- 2.8 ng/ml, respectively, P < 0.01). In the colitis patients, mean free IL-18 level and IL-18BP were significantly different between healthy individuals and patients, but not between disease remission and exacerbation (167 +/- 32, 492 +/- 247 and 451 +/- 69 pg/ml for IL-18, and 2.1 +/- 1.1, 7.69 +/- 4 and 6.8 +/- 7 ng/ml for IL-18BP, respectively, P= 0.05).
Conclusions:
IL-18 and IL-18BP levels are higher in patients with inflammatory bowel disease compared to healthy individuals. In Crohn's disease, but not in ulcerative colitis, IL-18 (but not free IL-18) and IL-18BP levels are significantly higher during exacerbation compared to remission. This observation highlights the importance of IL-18 in the pathogenesis of inflammatory bowel diseases, especially in Crohn's disease.
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