HMG-1 as a late mediator of endotoxin lethality in mice.
Science
; 285(5425): 248-51, 1999 Jul 09.
Article
em En
| MEDLINE
| ID: mdl-10398600
ABSTRACT
Endotoxin, a constituent of Gram-negative bacteria, stimulates macrophages to release large quantities of tumor necrosis factor (TNF) and interleukin-1 (IL-1), which can precipitate tissue injury and lethal shock (endotoxemia). Antagonists of TNF and IL-1 have shown limited efficacy in clinical trials, possibly because these cytokines are early mediators in pathogenesis. Here a potential late mediator of lethality is identified and characterized in a mouse model. High mobility group-1 (HMG-1) protein was found to be released by cultured macrophages more than 8 hours after stimulation with endotoxin, TNF, or IL-1. Mice showed increased serum levels of HMG-1 from 8 to 32 hours after endotoxin exposure. Delayed administration of antibodies to HMG-1 attenuated endotoxin lethality in mice, and administration of HMG-1 itself was lethal. Septic patients who succumbed to infection had increased serum HMG-1 levels, suggesting that this protein warrants investigation as a therapeutic target.
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Base de dados:
MEDLINE
Assunto principal:
Proteínas de Grupo de Alta Mobilidade
/
Proteínas de Transporte
/
Bacteriemia
/
Endotoxemia
/
Endotoxinas
/
Macrófagos
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos