ABSTRACT

Normal wound healing occurs by a sequence of events in which cellular, soluble factors, and matrix components act in concert to repair a wound. The healing re­ sponse can be described in four broad, overlapping phases-hemostasis, inflamma­ tion, proliferation, and remodeling.1 The disruption in the integrity o f the vascular endothelium activates the coagulation cascade, which results in the formation of a clot consisting of fibrin, platelets, and erythrocytes. The initial wound matrix of fibrin acts as a scaffold upon which inflammatory cells enter the wound.2 The injury also stimulates the release of various mediators o f cell-cell and cell-matrix interac­ tions, such as eicosanoids and cytokines. Eicosanoids are metabolites o f cell mem­ brane essential fatty acids and function mainly as messengers in the wound and initiate the signs and symptoms o f inflammation, such as redness, swelling, and pain. Included in this group are prostaglandins and thromboxanes, which are formed via the cyclooxygenase pathway, and leukotrienes, which are formed via the lipoxygenase pathway. Cytokines, such as platelet derived growth factor (PDGF) and transforming growth factor-ß (TGF-ß), are polypeptides that mediate the early inflammatory response but also modulate this and the immune response. Further­ more, cytokines are chemoattractants, mitogens and stimulators of extracellular matrix (ECM) deposition for cells that enter the wound.3 5 Initially, neutrophils are present in increased numbers and are important in phagocytosis of foreign material and bacteria. Shortly thereafter, monocytes migrate into the tissue, transform into mac­ rophages, and become the predominant inflammatory cell type. Similar to the neu­ trophils, macrophages continue to phagocytose foreign material and release various cytokines.6 Lymphocytes also appear in increased numbers in the wound at a de­ layed point and secret cytokines but are not able to phagocytose material. Studies have demonstrated that only the macrophage is critical for normal healing. How­ ever, all o f the cells contribute to the organized repair o f a wound by cleaning the wound site and releasing mediators o f cell-cell and cell-matrix interactions, such as eicosanoids and cytokines. In addition to that seen from the inflammatory cells, platelet aggregation and degranulation result in the release of cytokines. The ECM

The Biology and Practice o f Current N utritional Support, 2nd Edition, edited by Rifat Latifi and Stanley J. Dudrick. © 2003 Landes Bioscience.