Chronic glucocorticosteroid administration modulates the response of the fibrinolytic system to bacterial lipopolysaccharide

J. Schneiderman, R. Adar, M. Sawdey

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An in vivo rat model was used to study the effect of chronic glucocorticosteroid administration on the response of the fibrinolytic system to lipopolysaccharide (LPS). Male Lewis rats were injected subcutaneously for 30 consecutive days with either saline or saline containing 0.1 μg/g dexamethasone. On the thirty-first day, the rats were challenged with intraperitoneal injections of LPS (0.5 μg/g). Plasma and selected tissues (liver, kidney, heart, lung, muscle, and fat) were removed for analysis at various times after LPS injection. LPS treatment caused a rapid rise in plasma type 1 plasminogen activator inhibitor (PAW) activity in both groups. However, in the dexamethasone-pretreated animals a transient decline in PAI-1 activity was detected at 4 h, coinciding with a transient increase in plasma tissue plasminogen activator (t-PA) activity and a marked elevation of t-PA messenger RNA (mRNA) levels in the lung. Plasma t-PA activity returned below basal levels by 8 h and did not differ between the two groups at later times. At 24h, PAI-1 activity remained significantly elevated in the dexamethasone-pretreated rats while declining in the saline-pretreated rats. A greater induction of PAI-1 mRNA was evident in the dexamethasone-pretreated rats in all six tissues examined. Notably, a 3-fold greater increase in PAI-1 mRNA was detected in the liver at 24h, corresponding with the sustained elevation in plasma PAI-1 activity at this time. Collectively, these data suggest that chronic glucocorticosteroid treatment potentiates the induction of both t-PA and PAI-1 gene expression by LPS, resulting in an initial transient increase in plasma t-PA activity followed by a more sustained elevation in plasma PAI-1 activity.

Original languageEnglish
Pages (from-to)238-244
Number of pages7
JournalFibrinolysis and Proteolysis
Issue number4
StatePublished - Jul 1994


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