THE ROLE OF CYTOKINES AND ADHESION MOLECULES IN THE DEVELOPMENT OF INFLAMMATORY INJURY

Clinicians are constantly challenged by patients who demonstrate the i ll effects of an uncontrolled host inflammatory response. Patients wit h sepsis and adult respiratory distress syndrome (ARDS) are frequently encountered examples of this syndrome. Despite advances in intensive care, mortality from these syndromes remains unchanged over the past t wo decades. In order to gain a better understanding of this pathophysi ological response and to identify more specific therapeutic targets, t he techniques of molecular biology have been applied to in vivo inflam matory models. Recent data indicate that the inflammatory response is dependent on the presence of both cytokines and adhesion molecules tha t mediate neutuophil-endothelial cell adhesive interactions. In this a rticle, we review our experience using a lung model of inflammation th at has provided insight into the events leading to injury. Cytokines [ particularly, interleukin 1 (IL-1) and tumor necrosis factor alpha (TN F-alpha)], and endothelial, as well as leukocyte, adhesion molecules a ppear to coordinate a cascade of interactions between leukocytes and e ndothelial cells, which results in tissue injury.