Role of macrophages in the progression of acute pancreatitis

Abstract

In addition to pancreatic cells, other inflammatory cell populations contribute to the generation of inflammatory mediators during acute pancreatitis. In particular, macrophages could be activated by mediators released during pancreatitis by a damaged pancreas. It has been reported that peritoneal macrophages, alveolar macrophages and Kupffer cells become activated in different stages of severe acute pancreatitis. However, macrophages display remarkable plasticity and can change their physiology in response to environmental cues. Depending on their microenvironmental stimulation, macrophages could follow different activation pathways resulting in marked phenotypic heterogeneity. This ability has made these cells interesting therapeutical targets and several approaches have been assayed to modulate the progression of inflammatory response secondary to acute pancreatitis. However, despite the recent advances in the modulation of macrophage function in vivo, the therapeutical applications of these strategies require a better understanding of the regulation of gene expression in these cells.

Keywords: Inflammation; Macrophages; Pancreatitis; Systemic inflammatory response syndrome.

Figure 1

Depending on the microenvironment, macrophages could follow different activation processes. Classical M1 activation is induced by bacterial products or pro-inflammatory cytokines as tumor necrosis factor α or IFNγ. Regulatory M2b activation is induced by glucocorticoids, prostaglandins or interleukin (IL)-10. Finally, reparative M2a activation depends mainly on IL-4 and IL-13. Since these phenotypes could be redirected, the modulation of macrophage phenotype could be a promising therapeutical approach for the treatment of the systemic effects of acute pancreatitis. TNFα: Tumor necrosis factor α.