Introduction

Active episodes of inflammatory bowel disease (IBD; Crohn's disease, ulcerative colitis) are characterized by rectal bleeding, diarrhea, exudation, fever, abdominal pain, and weight loss. Histopathological examination of the inflamed gut reveals vasodilation, venocongestion, edema, infiltration of large numbers of inflammatory cells, erosions, and frank ulcerations. There is a growing body of experimental and clinical evidence suggesting that IBD may result from a dys-regulated immune response to components of the normal gut flora. Current theory suggests that the inability to regulate the normal T-cell-mediated immune responses to normal comensal bacteria gut flora results in activation of Thl-type CD4+ T-cells with subsequent release of proinflammatory mediators such as interleukins-2, -12, and -1b (IL-2, IL-12 and IL-lb, respectively), interferon-g (IFN-g), and tumor necrosis factor-a (TNF-a), as well as platelet activating factor (PAF), nitric oxide (NO), reactive oxygen species (ROS) and certain arachidonate metabolites [1] (Figure 1). Because many of these proinflammatory mediators are vasoactive and activate the microvascular endothelium, it is not surprising to find that much of the pathophysiology observed in the chronically inflamed gut may result from alterations in the colonic and/or intestinal microcirculation [2] (Figure 2). For example, some of these inflammatory mediators (e.g., histamine, bradykinin, NO, prostaglandins) possess potent vasodilatory properties and will increase blood flow (hyper-emia), thereby producing the characteristic erythema in the inflamed bowel. Increased arteriolar blood flow will also raise hydrostatic pressure in the downstream capillaries, resulting in transcapillary fluid movement across intestinal capillaries and inducing interstitial edema. Certain proin-flammatory cytokines (e.g., TNF-a, IFN-g, IL-12) expressed during T-cell and macrophage activation will activate venular endothelial cells to enhance the expression of certain vascular adhesion molecules that mediate leukocyte-endothelial interactions and subsequent emigration of leukocytes (PMNs, monocytes, and lymphocytes) into the surrounding tissue. Leukocyte emigration is often associated with vascular protein leakage with accumulation of albumin and other plasma proteins in the gut interstitium. The resultant increase in tissue oncotic pressure further promotes fluid filtration across capillaries and accelerates the development of interstitial edema. Taken together, these pathophysiological considerations suggest that the intestinal microcirculation contributes largely to the pathophysiology of chronic gut inflammation.

This brief review will summarize the current state of knowledge regarding the role of the microvasculature in chronic gut inflammation.

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