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Anti-CD14 mAb treatment provides therapeutic benefit after in vivo exposure to endotoxin.

ABSTRACT: The presence of endotoxin from Gram-negative bacteria signals the innate immune system to up-regulate bacterial clearance and/or killing mechanisms. Paradoxically, such responses also contribute to septic shock, a clinical problem occurring with high frequency in Gram-negative septicemia. CD14 is a receptor for endotoxin (lipopolysaccharide, LPS) and is thought to have an essential role in innate immune responses to infection and thereby in the development of septic shock. Using a novel rabbit model of endotoxic shock produced by multiple exposures to endotoxin, we show that anti-rabbit CD14 mAb, which blocks LPS-CD14 binding, protects against organ injury and death even when the antibody is administered after initial exposures to LPS. In contrast, anti-rabbit tumor necrosis factor mAb treatment fails to protect when administered after LPS injections. These results support the concept that anti-CD14 treatment provides a new therapeutic window for the prevention of pathophysiologic changes that result from cumulative exposures to LPS during septic shock in man.

SUBMITTER: Schimke J

PROVIDER: S-EPMC24941 | biostudies-literature | 1998 Nov

REPOSITORIES: biostudies-literature

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Anti-CD14 mAb treatment provides therapeutic benefit after in vivo exposure to endotoxin.

Schimke J J Mathison J J Morgiewicz J J Ulevitch R J RJ

Proceedings of the National Academy of Sciences of the United States of America 19981101 23

The presence of endotoxin from Gram-negative bacteria signals the innate immune system to up-regulate bacterial clearance and/or killing mechanisms. Paradoxically, such responses also contribute to septic shock, a clinical problem occurring with high frequency in Gram-negative septicemia. CD14 is a receptor for endotoxin (lipopolysaccharide, LPS) and is thought to have an essential role in innate immune responses to infection and thereby in the development of septic shock. Using a novel rabbit m ...[more]

PMID: 9811894

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Anti-CD14 mAb treatment provides therapeutic benefit after in vivo exposure to endotoxin.

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Anti-CD14 mAb treatment provides therapeutic benefit after in vivo exposure to endotoxin.

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