Prostaglandin E2 as a Mechanistic Biomarker of Chronic Pancreatitis

Introduction: Chronic pancreatitis (CP) is a disease associated with chronic inflammation, fibrosis and pain. There is a lack of tools available that facilitate early diagnosis, when intervention could prevent irreversible damage. Pilot data suggested prostaglandin E2 (PGE2) as a candidate biomarker for early CP. PGE2 activates signaling pathways that promote inflammation, pain, and fibrosis. Methods: We assessed PGE2, metabolites, and downstream targets in pancreatic fluid collected endoscopically 0-10 (n=110) and 10-20 (n=111) minutes after intravenous secretin administration. PGE2 and metabolites were measured in plasma (n=75) and urine (n=71) from the same subjects. Subjects were enrolled in the PROCEED study and classified symptomatic controls, acute/recurrent acute pancreatitis (AP/RAP), or CP. Results: A significant main effect was detected in 10-20 min pancreas fluid (p=0.027) and plasma (p=0.046); post-hoc testing showed PGE2 was lower in the AP/RAP group compared to symptomatic controls. There was also trend toward lower PGE2 in urine (p=0.062). To elucidate the active downstream pathways, calcitonin-gene related peptide, substance P, and matrix metalloproteinases (MMPs) 1, 2, 3, 7, 9, and 13 were measured in pancreas fluid. A significant difference between the three groups was detected for both MMP7 and MMP9. MMP7 was elevated in individuals with CP versus AP/RAP (p=0.012) for samples collected early, but both time points for MMP9 (p=0.027, p=0.002). Discussion: While PGE2 is detectable in pancreas fluid, these data suggest that it may not be sensitive enough to distinguish between AP/RAP and CP. However, MMPs may distinguish between stages of pancreatitis and require further testing as potential diagnostic biomarkers.