Characterization of the neurotrophic response to acute pancreatitis

Introduction: Interesting preliminary data on changes in the neurotrophin system in various digestive diseases have recently begun to emerge. Aims: To measure changes in messenger RNA (mRNA) levels of neurotrophins and to identify cell types expressing neurotrophins in the pancreas of rats with L-arginine-induced pancreatitis. Methodology: Rats were killed at time points from 2 hours to 4 weeks after the induction of pancreatitis, and responses were measured by assay. Results: By RNase protection assay, ciliary neurotrophic factor (CNTF) mRNA expression showed a rapid response (sixfold increase over control) in the inflamed pancreas at 2 hours. The levels of mRNA expression of brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), neurotrophin-3 (NT-3), and neurotrophin-4 (NT-4) in the inflamed pancreas reached a peak at 1 week (2.5-fold, twofold, fourfold, and fivefold increase, respectively). By immunohistochemistry, immunoreactivity for all neurotrophins examined was observed in the islets of Langerhans in the control pancreas at all time points, but it was markedly reduced in the islets in the inflamed pancreas at 2 and 6 hours. Acinar and ductal cells, inflammatory cells, and neural elements were immunoreactive for those neurotrophins in the inflamed pancreas from 2 hours to 2 weeks. Conclusion: The temporal and spatial expression of neurotrophins in the course of experimental pancreatitis suggests that their upregulation is a critical component of the response of the pancreas to injury in this model.