Prolyl Hydroxylase and Tissue Inhibitor of Metalloproteinase in Pure Pancreatic Juice in Patients with Chronic Pancreatitis

Prolyl hydroxylase is a key enzyme in collagen synthesis, and tissue inhibitor of metalloproteinase (TIMP) is known to suppress collagenolytic enzymes. To see whether the levels of these two enzymes in serum and human pure pancreatic juice (PPJ) are good indicators of pancreatic fibrosis in chronic pancreatitis (CP), we examined 15 controls, 14 alcoholics without evident pancreatic diseases (7 current drinkers and 7 former drinkers), and 19 patients with CP. Levels of the two enzymes were determined by a sandwich enzyme immunoassay method. TIMP-1 levels in PPJ were significantly higher in patients with CP than in controls and alcoholics, with overlap in only a few exceptional patients. A significant inverse correlation between TIMP-1 and bicarbonate output in PPJ was observed. Prolyl hydroxylase levels in PPJ, in contrast, were significantly higher in current drinkers than in patients with CP, controls, and former drinkers, with overlap in only a few exceptional patients with relapsing CP. Identical results were obtained even when the enzyme levels were expressed as nanograms per milligram of protein. Serum levels of prolyl hydroxylase and TIMP-1 showed no significant differences among controls, current alcoholics, former alcoholics, and patients with CP. These results indicate that the raised level of TIMP-1 in PPJ, unlike that of prolyl hydroxylase, is a good indicator of pancreatic fibrosis in CP.