Ruxolitinib, a JAK1/2 Inhibitor, Ameliorates Cytokine Storm in Experimental Models of Hyperinflammation Syndrome
| Autor: | Michael Peel, Rachel Bassett, Katherine Verbist, Kim E. Nichols, Sabrin Albeituni, Eduardo Huarte, Brittany Fay, Paul A. Smith |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Ruxolitinib medicine.medical_treatment RM1-950 JAK inhibition Proinflammatory cytokine 03 medical and health sciences 0302 clinical medicine Immune system medicine Pharmacology (medical) Pharmacology Hemophagocytic lymphohistiocytosis business.industry Organ dysfunction cytokine storm syndrome cytokine release syndrome Brief Research Report medicine.disease Cytokine release syndrome 030104 developmental biology Cytokine hemophagocytic lymphohistiocytosis 030220 oncology & carcinogenesis Immunology Therapeutics. Pharmacology medicine.symptom business Cytokine storm hyperinflammatory syndromes medicine.drug |
| Zdroj: | Frontiers in Pharmacology Frontiers in Pharmacology, Vol 12 (2021) |
| ISSN: | 1663-9812 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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