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ACS Applied Materials & Interfaces

ACS Applied Materials & Interfaces

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Use of the JAK Inhibitor Ruxolitinib in the Treatment of Hemophagocytic Lymphohistiocytosis.

Published:16 February 2021 DOI: 10.3389/fimmu.2021.614704 PMID: 33664745
Camille Keenan, Kim E Nichols, Sabrin Albeituni

Abstract

Hemophagocytic lymphohistiocytosis (HLH) is a rare hyperinflammatory syndrome driven by overactive T cells and macrophages that abundantly secrete numerous pro-inflammatory cytokines, including interferon (IFN)-gamma, interleukin (IL)-1-beta, IL-2, IL-6, IL-10, IL-18, and tumor necrosis factor (TNF). The release of these and other cytokines underlies many of the clinical and pathologic manifestations of HLH, which if left untreated, can lead to multi-organ failure and death. The advent of etoposide-based regimens, such as the Histiocyte Society HLH-94 and HLH-2004 protocols, has substantially decreased the mortality associated with HLH. Nevertheless, the 5-year survival remains low at ~60%. To improve upon these results, studies have focused on the use of novel cytokine-directed therapies to dampen inflammation in HLH. Among the agents being tested is ruxolitinib, a potent inhibitor of the Janus Kinase (JAK) and Signal Transducer and Activation of Transcription (STAT) pathway, which functions downstream of many HLH-associated cytokines. Here, we review the basic biology of HLH, including the role of cytokines in disease pathogenesis, and discuss the use of ruxolitinib in the treatment of HLH.

Substances (9)

Related products
Procduct Name CAS Molecular Formula Supplier Price
Etoposide 33419-42-0 C29H32O13 693 suppliers $9.00-$17300.00
Acid Red 94 632-69-9 C20H5Cl4I4NaO5 474 suppliers $10.00-$979.00
Ruxolitinib 941678-49-5 C17H18N6 460 suppliers $10.00-$2757.40
HUMAN IL-2 110942-02-4 94 suppliers $80.00-$1020.00
MOUSE IL-10 76 suppliers Inquiry
MOUSE IL-6 71 suppliers $75.00-$1824.00
IL-18 57 suppliers Inquiry
Interleukin (IL)-6 Receptor C??H??N??O?? 20 suppliers Inquiry
Interferon-g (IFN-g) 4 suppliers Inquiry

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