Ruxolitinib, a JAK1/2 Inhibitor, Ameliorates Cytokine Storm in Experimental Models of Hyperinflammation Syndrome
| العنوان: | Ruxolitinib, a JAK1/2 Inhibitor, Ameliorates Cytokine Storm in Experimental Models of Hyperinflammation Syndrome |
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| المؤلفون: | Michael Peel, Rachel Bassett, Katherine Verbist, Kim E. Nichols, Sabrin Albeituni, Eduardo Huarte, Brittany Fay, Paul A. Smith |
| المصدر: | Frontiers in Pharmacology Frontiers in Pharmacology, Vol 12 (2021) |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 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 |
| الوصف: | 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. |
| تدمد: | 1663-9812 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c30f487046b78dfa8c538d8847778cf6 https://pubmed.ncbi.nlm.nih.gov/33981229 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....c30f487046b78dfa8c538d8847778cf6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16639812 |
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