Glucocorticoids inhibit type I IFN beta signaling and the upregulation of CD73 in human lung
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LETTER
Glucocorticoids inhibit type I IFN beta signaling and the upregulation of CD73 in human lung Juho Jalkanen1, Ville Pettilä2, Teppo Huttunen3, Maija Hollmén4 and Sirpa Jalkanen4,5* © 2020 The Author(s)
Dear Editor, Glucocorticoids are widely used to treat acute respiratory distress syndrome (ARDS) despite their use being highly controversial based on randomized controlled trials and meta-analyses [1]. As type I interferons (IFNs) are our first line of defense against severe viral respiratory infections, we explored whether glucocorticoids interfere with IFN signaling and whether their use associates with outcome of IFN beta treatment of ARDS. Methods are described in the eSupplement. We performed a propensity-matched post hoc analysis using data from the recent randomized INTEREST trial comparing IFN beta-1a to placebo in ARDS patients [2]. Seventy-eight out of 144 patients (54%) included in the IFN beta-1a treatment arm of the INTEREST trial received glucocorticoids during the 28-day study period, 56% (44/78) at randomization (D0), 27% (21/78) during the treatment (D1–6) and 17% (13/78) after the treatment (D7 onward). Day-28 mortality for patients receiving glucocorticoids with IFN beta-1a was 39.7% compared to 10.6% for patients receiving IFN beta-1a alone. The Kaplan–Meier curves of the IFN beta-1a treatment arm adjusted by ARDS severity and divided according to the overlapping (D0–D6) use of glucocorticoids with IFN beta-1a treatment demonstrate significantly increased mortality by glucocorticoid use (p = 0.0002, see supplement). In the post hoc propensity-matched analysis of the IFN beta-1a arm (n = 144), baseline systemic glucocorticoid *Correspondence: [email protected] 4 Medicity Research Laboratory, University of Turku, Turku, Finland Full author information is available at the end of the article Juho Jalkanen, Ville Pettilä, Maija Hollmén and Sirpa Jalkanen have contributed equally to this work.
treatment was independently associated with D28 mortality (OR 5.4, 95% CI 2.1–13.9, p
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