Ruxolitinib, a JAK1/2 Inhibitor, Ameliorates Cytokine Storm in Experimental Models of Hyperinflammation Syndrome
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 proinflam...
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| Main Authors: | , , , , , , , |
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| Format: | Book |
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Frontiers Media S.A.,
2021-04-01T00:00:00Z.
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| Online Access: | Connect to this object online. |
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| Summary: | 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. |
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| Item Description: | 1663-9812 10.3389/fphar.2021.650295 |