Peptide YY improves local and systemic parameters and prevents death in lethal necrotizing pancreatitis

Peptide YY (PYY) is a gastrointestinal hormone with multiple inhibitory effects on the proximal digestive tract, including suppression of secretion by the exocrine pancreas.

To determine whether peptide YY would reduce mortality in a lethal model of necrotizing pancreatitis by improving local and systemic parameters of this disease.

Necrotizing pancreatitis was induced in three groups of 30 mice by feeding a choline-deficient ethionine-supplemented diet. Osmotic pumps placed in 10 control mice delivered normal saline. In the two study groups, PYY was delivered at 200 pmol/kg/hr. The prophylactic group received PYY pumps at the onset; the therapeutic group received pumps 24 hours later. Ten mice from each group were followed to assess survival. Remaining mice were killed at 24, 48, 72, and 96 hours. Pancreata were graded on a nine-point histologic scale. Amylasemia was quantified by kinetic determination. Serum interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) values were determined by ELISA.

Both prophylactic and therapeutic PYY significantly reduced mortality compared with that seen in controls ( p = 0.05 and p = 0.007). Five-day survival was 33% in controls, 80% in those receiving prophylactic PYY, and 100% in the therapeutic group. Amylasemia was reduced in the therapeutic group by day 3 ( p < 0.02) and in the prophylactic group by day 4 ( p < 0.01). Histologic changes mirrored those in serum amylase. Prophylactic and therapeutic administration of PYY suppressed early circulating levels of IL-6.

PYY reduces mortality and improves local and systemic parameters in this murine model and may be of clinical benefit in the management of human necrotizing pancreatitis, particularly as this study demonstrates a clear survival benefit when PYY is given after the onset of disease.