The role of cytokines and adhesion molecules in the development of inflammatory injury.
Clinicians are constantly challenged by patients who demonstrate the ill effects of an uncontrolled host inflammatory response. Patients with 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 two decades. In order to gain a better understanding of this pathophysiological response and to identify more specific therapeutic targets, the techniques of molecular biology have been applied to in vivo inflammatory models. Recent data indicate that the inflammatory response is dependent on the presence of both cytokines and adhesion molecules that mediate neutrophil-endothelial cell adhesive interactions. In this article, we review our experience using a lung model of inflammation that has provided insight into the events leading to injury. Cytokines [particularly, interleukin 1 (IL-1) and tumor necrosis factor alpha (TNF-alpha)], and endothelial, as well as leukocyte, adhesion molecules appear to coordinate a cascade of interactions between leukocytes and endothelial cells, which results in tissue injury.
Shanley
T P
TP
University of Michigan Medical School, Department of Pathology, Ann Arbor.
Warner
R L
RL
Ward
P A
PA
D000818:Animals; D018821:CD18 Antigens / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000502:physiology*; D016207:Cytokines / Q000502:physiology*; D004727:Endothelium / Q000166:cytology; D006801:Humans; D007249:Inflammation / Q000378:metabolism* / Q000503:physiopathology*; D007962:Leukocytes; D008168:Lung / Q000378:metabolism; D055370:Lung Injury; D019001:Nitric Oxide Synthase / Q000378:metabolism; D019087:Selectins / Q000378:metabolism; D015854:Up-Regulation
D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D019087:Selectins; D019001:Nitric Oxide Synthase