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Citations to this article

Interferon-gamma overcomes glucocorticoid suppression of cachectin/tumor necrosis factor biosynthesis by murine macrophages.
C E Luedke, A Cerami
C E Luedke, A Cerami
Published October 1, 1990
Citation Information: J Clin Invest. 1990;86(4):1234-1240. https://doi.org/10.1172/JCI114829.
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Interferon-gamma overcomes glucocorticoid suppression of cachectin/tumor necrosis factor biosynthesis by murine macrophages.

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Abstract

Glucocorticoids almost completely inhibit the synthesis by isolated macrophages of cachectin/tumor necrosis factor (TNF), a cytokine implicated as a major endogenous mediator of septic shock. Despite this in vitro effectiveness, the clinical use of glucocorticoids has failed to demonstrate any clear benefit in the treatment of septic shock. In an effort to understand what other mechanisms might play a role in the patient with sepsis, we examined the effect of interferon-gamma (IFN gamma) on the synthesis of cachectin/TNF. We show here that IFN gamma, although unable by itself to induce cachectin/TNF synthesis, enhanced the endotoxin-induced production of cachectin/TNF in vitro. Furthermore, IFN gamma overcame the inhibition of cachectin/TNF synthesis caused by the glucocorticoid, dexamethasone. These effects of IFN gamma were accounted for by increased levels of cachectin/TNF mRNA. The in vivo implications of these studies are discussed with emphasis on their relevance in human sepsis.

Authors

C E Luedke, A Cerami

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Total citations by year

Year: 2024 2021 2020 2019 2012 2010 2006 2005 2003 2002 2001 2000 1999 1998 1997 1996 1995 1994 1993 1992 1991 1988 Total
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