Role of Cytokines in Intestinal Health and Disease
The intestinal mucosa is a complex of cells responsible for nutrient and fluid adsorption, secretion of digestive enzymes, sampling of immunogens from the lumen, and provision of a protective barrier to the plethora of microorganisms colonizing the intestinal tract. The normal function of the epithelial layer and the underlying lamina propria requires that the interaction between this variety of cells be balanced and closely regulated. This homeostasis may rely on the proper concentrations of a variety of intercellular messengers acting in autocrine and paracrine fashions to ensure proper cellular functions. These messengers include vasoactive peptides, chemotactic peptides, neuropeptides, prostaglandins, leukotrienes, and cytokines (1). All of these factors can be described as intercellular hormones, a concept first introduced by Sir Ernest Starling in 1905 (2). He described hormones as chemical messengers that could either increase the activity or increase the growth of a cell, tissue, or organ (2,3). These factors can be detected in healthy, as well as diseased, tissue; however, during an inflammatory response, the physiological concentrations of many intercellular hormones are altered. For example, increases in the levels of the 334proinflammatory cytokines [e.g., tumor necrosis factor (TNF), interleukin 1 (IL-1), and interleukin 6 (IL-6)] will enhance the migration of neutrophils (PMNs) and macrophages into the tissue to eliminate infectious agents or remove cellular debris caused by tissue destruction.