Can we protect the gut in critical illness? The role of growth factors and other novel approaches

Abstract

The intestine plays a central role in the pathophysiology of critical illness and is frequently called the "motor" of the systemic inflammatory response. Perturbations to the intestinal barrier can lead to distant organ damage and multiple organ failure. Therefore, identifying ways to preserve intestinal integrity may be of paramount importance. Growth factors and other peptides have emerged as potential tools for modulation of intestinal inflammation and repair due to their roles in cellular proliferation, differentiation, migration, and survival. This review examines the involvement of growth factors and other peptides in intestinal epithelial repair during critical illness and their potential use as therapeutic targets.

Figure 1

A simplified model of epithelial injury and restitution. Following epithelial injury, cells depolarize, dedifferentiate, and migrate to cover the denuded area (restitution). Once the epithelial defect is sealed, epithelial cell proliferation is stimulated to replace the cell pool. Epithelial cells then differentiate and mature to become an intact epithelial layer again.

Figure 2

Several growth factors are involved in preventing or enhancing intestinal epithelial repair. HGF, hepatocyte growth factor; EGF, epidermal growth factor; IGF, insulin-like growth factor; HB-EGF, heparin binding EGF-like growth factor; KGF, keratinocyte growth factor; GLP-2, glucagon-like peptide-2; TFF, trefoil factor family; ITF, intestinal trefoil factor