S. A. Morrison1, S. Hamarneh1, H. Sturgeon1, D. Hu1, H. Huo1, W. Zhang1, K. Economopoulos1, S. Gul1, F. Adiliaghdam1, J. Ramirez Decrescenzo1, R. Hodin1 1Massachusetts General Hospital,Surgery,Boston, MA, USA
Introduction: Inflammatory Bowel Disease (IBD) remains a chronic disease of major clinical significance secondary to its increasing prevalence and morbidity worldwide. While the exact mechanistic pathogenesis of IBD remains elusive, its origins are known to be both complex and multi-factorial; involving variants in gene expression, exposure to environmental agents, and a dysregulated immune response. At the heart of suspected disease expression lies the tenet that aberrant gut-derived immune factors play a central role in pathogenesis. This work is based on the hypothesis that potential decreased expression of the brush border enzyme, Intestinal Alkaline Phosphastase, known for its anti-inflammatory properties, may contribute to disease development in these populations.
Methods: Colonic biopsy samples were obtained from 17 patients with Inflammatory Bowel Disease, as well as from 10 healthy controls. In IBD patients, specimens were obtained both from inflamed and non-inflamed areas. Inflammatory cytokine levels and IAP mRNA was determined by quantitative reverse transcription-polymerase chain reaction.
Results:When compared with tissue from healthy controls, IAP mRNA expression was decreased in both inflamed and non-inflamed samples taken from patients with Ulcerative Colitis (UC), with the most significant decrease seen in inflamed tissue( Healthy Controls: 1.15, UC non-inflamed 0.85 (p=0.07), UC inflamed 0.19 (p=0.01)) . In a smaller sample size, tissue samples from Crohn’s patients did not reveal a significant difference in IAP expression when compared to healthy controls (Healthy Controls: 1.15, Crohn’s disease inflamed and non-inflamed: 1.16, 1.02). Inflammatory cytokines TNF-alpha and IL-8 were higher in IBD patients, specifically in inflamed tissue, with expression in Ulcerative Colitis patients being particularly high, correlating to lower levels of IAP, a gut derived anti-inflammatory enzyme (IL-8: HC 0.82, CD non-inflamed and inflamed 8.4 and 276 (p=0.2 and 0.002), UC non-inflamed and inflamed 22.5 and 3441 (p=0.06 and 0.007) TNF-a: HC 0.91, CD non-inflamed and inflamed 1.76 and 6.24 (p=0.05 and 0.006), UC non-inflamed and inflamed 9.17 and 47.3 (p=0.002 and p=0.01)).
Conclusion: Decreased levels of IAP expression, correlating with increased cytokine levels in the inflamed mucosa of patients with Ulcerative Colitis may indicate a role for the enzyme in disease pathogenesis and could lay groundwork for use of this agent as a therapeutic modality in future clinical studies.
