{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T07:14:34Z","timestamp":1792394074516,"version":"4.4.0"},"reference-count":69,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,2,16]],"date-time":"2021-02-16T00:00:00Z","timestamp":1613433600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3389\/fimmu.2021.614704","type":"journal-article","created":{"date-parts":[[2021,2,18]],"date-time":"2021-02-18T20:22:38Z","timestamp":1613679758000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":173,"title":["Use of the JAK Inhibitor Ruxolitinib in the Treatment of Hemophagocytic Lymphohistiocytosis"],"prefix":"10.3389","volume":"12","author":[{"given":"Camille","family":"Keenan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim E.","family":"Nichols","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrin","family":"Albeituni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,2,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1016\/j.blre.2007.05.001","article-title":"Hemophagocytic syndromes","volume":"21","author":"Janka","year":"2007","journal-title":"Blood Rev"},{"key":"B2","doi-asserted-by":"publisher","first-page":"135","DOI":"10.1016\/j.blre.2014.03.002","article-title":"Hemophagocytic syndromes\u2013an update","volume":"28","author":"Janka","year":"2014","journal-title":"Blood Rev"},{"key":"B3","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1111\/j.1547-5069.2009.01330.x","article-title":"What is patient safety culture? 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