Essential role of monocytes and macrophages in the progression of acute pancreatitis

Abstract

Acute pancreatitis (AP) is an inflammatory condition of the pancreas caused by an imbalance in factors involved in maintaining cellular homeostasis. Earliest events in AP occur within acinar cells accompanied by other principal contributors to the inflammatory response i.e. the endothelial cells, immunocytes (granulocytes, monocytes/macrophages, lymphocytes) and neutrophils. Monocytes/macrophages are important inflammatory mediators, involved in the pathophysiology of AP, known to reside in the peritoneal cavity (in the vicinity of the pancreas) and in peripancreatic tissue. Recent studies suggested that impaired clearance of injured acini by macrophages is associated with an altered cytokine reaction which may constitute a basis for progression of AP. This review focuses on the role of monocytes/macrophages in progression of AP and discusses findings on the inflammatory process involved.

Figure 1

Our current understanding of the role of monocytes and macrophages in the pathogenesis of acute pancreatitis. Local inflammation in the pancreas leads to secretion of pro-inflammatory cytokines and some unknown factors. These inflammatory mediators activate peritoneal macrophages (PMO), Kupffer cells, and alveolar macrophages (AMO), which if uncontrolled can cause multiple organ dysfunction syndrome (MODS). PMO display a classical M1 type activation in acute pancreatitis thus supporting the inflammatory process. TNF: Tumor necrosis factor; RNI: Reactive nitrogen intermediates; ROI: Reactive oxygen intermediates; PAAF: Pancreatitis associated ascitic fluid; PAP: Pancreatitis-associated protein; MCP: Monocyte chemotactic protein-1; PG: Prostaglandins; LK: Leukotrienes; SIRS: Systemic inflammatory response syndrome; PMN: Polymorphonuclear leukocytes; MIP: Macrophage inflammatory protein.