Interleukin-18 and its binding protein in patients with inflammatory bowel disease during remission and exacerbation

Abstract

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.