Glucocorticoid-mediated repression of cytokine gene transcription in human arteritis-SCID chimeras

The Journal of Clinical Investigation
A BrackJ J Goronzy

Abstract

Giant cell arteritis (GCA) is a vasculitic syndrome that preferentially affects medium and large-sized arteries. Glucocorticoid therapy resolves clinical symptoms within hours to days, but therapy has to be continued over several years to prevent disease relapses. It is not known whether and how glucocorticoids affect the function of the inflammatory infiltrate or why the disease persists subclinically despite chronic treatment. GCA is self-sustained in temporal arteries engrafted into SCID mice, providing a model in which the mechanisms of action and limitations of glucocorticoid therapy can be examined in vivo. Administration of dexamethasone to temporal artery-SCID chimeras for 1 wk induced a partial suppression of T cell and macrophage function as indicated by the reduced tissue concentrations of IL-2, IL-1beta, and IL-6 mRNA, and by the diminished expression of inducible NO synthase. In contrast, synthesis of IFN-gamma mRNA was only slightly decreased, and expression of TGF-beta1 was unaffected. These findings correlated with activation of the IkappaBalpha gene and blockade of the nuclear translocation of NFkappaB in the xenotransplanted tissue. Dose-response experiments suggested that steroid doses currently used in clini...Continue Reading

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Citations

Feb 20, 1999·Arthritis and Rheumatism·A BrackC M Weyand
Feb 13, 2002·Arthritis and Rheumatism·Cornelia M WeyandJörg J Goronzy
May 4, 2005·Zeitschrift für Rheumatologie·P M AriesW L Gross
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