Bioactive IL-18 expression is up-regulated in Crohn's disease

Area of Science:

• Immunology
• Gastroenterology
• Molecular Biology

Background:

• Crohn's disease (CD) involves uncontrolled mucosal T helper 1 (Th1) cell activation due to immunoregulatory factor imbalance.
• Interleukin-18 (IL-18), a cytokine derived from macrophage-like cells, plays a role in Th1 development and interferon-gamma (IFN-gamma) production.

Purpose of the Study:

• To investigate the expression and potential role of IL-18 in Crohn's disease (CD).

Main Methods:

• Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis were used to assess IL-18 expression.
• Samples included mucosal intestinal tissue and lamina propria mononuclear cells (LPMC) from CD patients, ulcerative colitis (UC) patients, and non-inflammatory bowel disease (IBD) controls.
• IL-18 activity was confirmed using IL-18 antisense oligonucleotides in CD LPMC cultures.

Main Results:

• Increased IL-18 mRNA accumulation was observed in both mucosal and LPMC samples from CD patients compared to UC and controls.
• Mature 18-kDa IL-18 was predominantly found in CD mucosal samples, while a 24-kDa precursor was seen in controls.
• Active interleukin-1 beta-converting enzyme (ICE) was detected in CD and UC samples, unlike controls where only the precursor was found.
• Down-regulation of IL-18 in CD LPMC cultures led to decreased IFN-gamma expression.

Conclusions:

• IL-18 upregulation is a significant feature of Crohn's disease (CD).
• The findings suggest that IL-18 contributes to the local immunoinflammatory response in CD.