Natural history of long-term lung injury in mouse experimental pancreatitis

In patients suffering from acute pancreatitis, the pathogenesis of pancreatitis-associated lung injury is not completely understood. Several rodent models of pancreatitis-associated lung injury suggested that activated neutrophils and the release of proinflammatory mediators after the activation of inflammatory cells within the pancreas might play an important role in translating the pancreatic inflammation to the lungs. In this study, we examined the natural history of pancreatitis-associated lung injury during an entire week.

Mice were administered 12 hourly intraperitoneal injections of a supramaximal dose of cerulein.

The severity of pancreatitis was time-dependent, with a maximal injury by 12-24 hrs after the start of cerulein administration. Pancreatitis was associated with a significant lung injury characterized by a rise in lung microvascular permeability, sequestration of neutrophils within the lungs, and a marked thickening of alveolar membranes. Within the lungs, the peak of macrophage inflammatory peptide-2, which attracts inflammatory cells within the injured area, preceded the peaks of both tumor necrosis factor-alpha and intercellular adhesion molecule-1. Moreover, histologic injury peaked by 12 hrs, with a full recovery at day 7. Serum macrophage inflammatory peptide-2 concentrations were significantly correlated with the occurrence of pulmonary leakage. Lung macrophage inflammatory peptide-2 concentrations peaked 12 hrs before pancreatic concentrations.

Mediators released by the pancreas into the blood during acute pancreatitis induce within the lungs the chronological expression of macrophage inflammatory peptide-2, tumor necrosis factor-alpha, and intercellular adhesion molecule-1.