1. Ruxolitinib, a JAK1/2 Inhibitor, Ameliorates Cytokine Storm in Experimental Models of Hyperinflammation Syndrome.
- Author
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Huarte E, Peel MT, Verbist K, Fay BL, Bassett R, Albeituni S, Nichols KE, and Smith PA
- Abstract
Hyperinflammatory syndromes comprise a heterogeneous group of disorders characterized by severe inflammation, multiple organ dysfunction, and potentially death. In response to antigenic stimulus (e.g., SARS-CoV-2 infection), overactivated CD8+ T-cells and macrophages produce high levels of proinflammatory cytokines, such as IFN-γ, TNF-α, IL-6, and IL-12. Multiple inflammatory mediators implicated in hyperinflammatory syndromes utilize the Janus kinase-signal transducers and activators of transcription (JAK-STAT) cascade to propagate their biological function. Our findings demonstrate that oral ruxolitinib dosing designed to mimic clinically relevant JAK-STAT pathway inhibition significantly reduces the harmful consequences of immune overactivation in multiple hyperinflammatory models. In contrast to monoclonal antibody therapies targeting a single cytokine, ruxolitinib effectively downregulates the functional effect of multiple cytokines implicated in hyperinflammatory states, without broad immunosuppression., Competing Interests: The authors declare that this study received funding from Incyte Corporation. The funder had the following involvement with the study: EH, MP, BF and PS are employees and shareholders of Incyte Corporation, and they conceived, performed and analyzed experiments, and wrote the manuscript. The handling editor declared a past co-authorship with one of the authors EH., (Copyright © 2021 Huarte, Peel, Verbist, Fay, Bassett, Albeituni, Nichols and Smith.)
- Published
- 2021
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