MONOCYTES-MACROPHAGES MEDIATE RECOVERY FROM ACUTE PANCREATITIS

Abstract

Background: Pancreatic fibrosis has been observed during the early phases of many acute pancreatitis models and it probably also occurs during the early stages of clinical acute pancreatitis as well. During recovery from acute pancreatitis, that fibrosis and its associated inflammation resolve and the gland re-acquires is pre-morbid morphology. Little is known regarding the events or players which are responsible for the resolution of acute pancreatitis. Aim: To determine if monocytes-macrophages play critical roles in mediating recovery from acute pancreatitis. Methods: Acute pancreatitis was induced by administration of caerulein or by ductal infusion with taurocholate and monocytes-macrophages were depleted in some animals by administration of diphtheria toxin (DT)1 day later. The animals were sacrificed on day 1 (i.e. before DT treatment) or day 7 after induction of pancreatitis. H&E and Sirius red-stained pancreatic sections were examined by an unbiased observer. Collagen deposition in the pancreas was quantitated by measuring tissue HO-proline levelzs. Results: Pancreatic inflammation and fibrosis were observed 1 day after induction of pancreatitis but, in non-DT treated animals, that inflammation and fibrosis had completely resolved by day 7. In contrast, marked inflammation, extensive fibrosis, and markedly elevated tissue HO-proline levels were still observed in DT-treated animals 7 days after induction of pancreatitis. Conclusions: By mediating anti-inflammatory and anti-fibrotic events in the pan-creas, monocytes-macrophages play a critical role in facilitating recovery from acute pancreatitis. When monocytes-macrophages are depleted or, presumably, if their function is reduced, the inflammatory and fibrotic changes that appear during the acute, formative, phase of pancreatitis persist and changes typical of chronic pancreatitis are noted.