title: Tumor necrosis factor mediates disseminated intravascular inflammation (DII) in the genesis of multiple organ edema.
abstract: Multiple system organ failure (MSOF), resulting from a diffuse overwhelming inflammatory response, is frequently the cause of death in patients suffering either severe injury or infection. Previous studies have demonstrated increased circulating levels of tumor necrosis factor with both severe injury and infection. In addition, the intravenous administration of tumor necrosis factor (TNF) has been shown to induce systemic responses similar to those seen in patients with MSOF. The data from in vitro studies suggest that TNF-mediated events at the level of the microcirculation may be primary in the genesis of multiple system organ edema and dysfunction. We hypothesized that the intravenous administration of TNF would acutely induce alterations in the microcirculation that were associated with the development of multiple organ edema and cardiorespiratory impairment. The cremaster microcirculation model was used to quantitate changes in microvascular indices. We directly observed increased numbers of firmly adherent leukocytes to the microvascular endothelium and quantitated decreased leukocyte rolling along the surface of the endothelium as leukocytes became firmly adherent following TNF injection. This TNF-mediated leukocyte-endothelial adherence was also associated with the development of microvascular protein leakage. TNF also acutely induced arteriolar vasodilation and increased microvascular blood flow. These changes in microvascular parameters were associated with the synchronous development of TNF-mediated multiple organ edema and cardiorespiratory impairment. These data support the hypothesis that TNF acutely mediates disseminated intravascular inflammation resulting in multiple organ edema and subsequent hemodynamic instability.
authors: Department of Surgery, University of Louisville School of Medicine, Kentucky 40292.
authors: M J
authors: MJ
authors: Edwards
authors: B T
authors: BT
authors: Heniford
authors: F N
authors: FN
authors: Miller
mesh_terms: D000818:Animals; D004487:Edema / Q000209:etiology*; D004730:Endothelium, Vascular / Q000473:pathology; D006439:Hemodynamics / Q000187:drug effects; D007275:Injections, Intravenous; D008297:Male; D008833:Microcirculation; D009132:Muscles / Q000098:blood supply; D051381:Rats; D017207:Rats, Sprague-Dawley; D012119:Respiration / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology / Q000502:physiology*; D014657:Vasculitis / Q000150:complications* / Q000473:pathology / Q000503:physiopathology; D014664:Vasodilation
chemical_list: D014409:Tumor Necrosis Factor-alpha