Chemokines as therapeutic targets in systematic inflammatory response syndrome

Abstract

Exaggerated systemic inflammatory response syndrome may lead to multiple organ dysfunction, organ failure and eventually death. Chemokines, a large family of small chemotactic cytokines, are critical inflammatory mediators in the development of both acute pancreatitis and sepsis. The present study has shown that blockage of CCR1 by a small molecule CCR1 antagonist has protective effect against acute lung injury in animal models of acute pancreatitis and sepsis. Depletion of mast cells by compound 48/80 has also attenuated acute pancreatitis-associated lung injury and sepsis-associated lung injury by attenuating the levels of chemokines. Treatment with an exogenous CX3C chemokine FTK has shown pro-inflammatory effect in acute pancreatitis-associated lung injury and anti-inflammatory effect against sepsis-associated lung injury. These promising findings validate that manipulating chemokine system may have protective effect in systemic inflammatory response syndrome.