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Dissociation between systemic and pulmonary anti-inflammatory effects of dexamethasone in humans
AuthorJilma, Bernd ; Prosch, Helmut ; Schwameis, Michael ; Schoergenhofer, Christian ; Derhaschnig, Ulla ; Stiebellehner, Leopold ; Bartko, Johann
Published in
British Journal of Clinical Pharmacology, Hoboken, 2016, Vol. 81, Issue 5, page 865-877
PublishedHoboken : Wiley-Blackwell, 2016
Document typeJournal Article
Keywords (EN)acute respiratory distress syndrome / dexamethasone / lipopolysaccharide / lung inflammation / surfactant protein d / respiratory-distress-syndrome / human alveolar macrophage / acute lung injury / human endotoxemia / methylprednisolone infusion / glucocorticoid sensitivity / inhaled lipopolysaccharide / inflammatory responses / healthy-subjects
Project-/ReportnumberF 5404-B21
URNurn:nbn:at:at-ubmuw:3-1443 Persistent Identifier (URN)
 The work is publicly available
Dissociation between systemic and pulmonary anti-inflammatory effects of dexamethasone in humans [0.53 mb]
Abstract (English)

AIMS The local pulmonary inflammatory response has a different temporal and qualitative profile compared with the systemic inflammatory response. Although glucocorticoids substantially downregulate the systemic release of acute-phase mediators, it is not clear whether they have comparable inhibitory effects in the human lung compartment. Therefore, we compared the anti-inflammatory effects of a pure glucocorticoid agonist, dexamethasone, on bronchoalveolar lavage and blood cytokine concentrations in response to bronchially instilled endotoxin. METHODS In this randomized, double-blind and placebo-controlled trial, 24 volunteers received dexamethasone or placebo and had endotoxin instilled into a lung segment and saline instilled into a contralateral segment, followed by bronchoalveolar lavage. RESULTS Bronchially instilled endotoxin induced a local and systemic inflammatory response. Dexamethasone strongly blunted the systemic interleukin (IL) 6 and C-reactive protein release. In sharp contrast, dexamethasone left the local release of acute-phase mediators in the lungs virtually unchanged: bronchoalveolar lavage levels of IL-6 were only 18% lower and levels of IL-8 were even higher with dexamethasone compared with placebo, although the differences between treatments were not statistically significant (P = 0.07 and P = 0.08, respectively). However, dexamethasone had inhibitory effects on pulmonary protein extravasation and neutrophil migration. CONCLUSIONS The present study demonstrated a remarkable dissociation between the systemic anti-inflammatory effects of glucocorticoids and its protective effects on capillary leak on the one hand and surprisingly low anti-inflammatory effects in the lungs on the other.

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