Role of neurogenic inflammation in the pathogenesis of acute pancreatitis and associated lung injury

Tachykinins and neurokinin receptors are implicated in the neurogenic inflammation (NI) during acute pancreatitis (AP). The effects of neurokinin receptor antagonists on caerulein-induced AP in mouse were investigated. NK1R antagonist, CP96,345, significantly reduced the severity of AP and associated lung injury. Present study demonstrated that CP96,345 treatment affected the release of substance P (SP), the expression of neurokinin receptor and tachykinin genes, and the expression of various adhesion molecules, in pancreas and lungs. A similar expression pattern was seen by immunohistochemical reactivity. Our results suggested a differential pattern of regulation of inflammatory response in pancreas and lungs. Finally, leukocyte-endothelial interaction in pancreatic microcirculation was visualized using intravital microscopy. CP96,345 significantly decreases the number of rolling and adherent leukocytes. In summary, blockade of SP-NK1R system, the major component of NI, has been proven to be effective in the treatment of AP and associated lung injury in mouse.

Author dc:creator

• LAU HON YEN

• acute pancreatitis, neurogenic inflammation, neurokinin receptor, tachykinin, pancreas, lung