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JAK Inhibitors in Cytokine Storm Syndromes.
Keenan, Camille; Albeituni, Sabrin; Nichols, Kim E; Hines, Melissa.
Afiliación
  • Keenan C; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Albeituni S; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Nichols KE; Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  • Hines M; Department of Pediatric Medicine, Division of Critical Care Medicine, St. Jude Children's Research Hospital, Memphis, TN, USA. Melissa.Hines@Stjude.org.
Adv Exp Med Biol ; 1448: 583-600, 2024.
Article en En | MEDLINE | ID: mdl-39117841
ABSTRACT
Cytokine storm syndromes (CSSs) comprise a group of severe and often fatal hyperinflammatory conditions driven by the overproduction of pro-inflammatory cytokines by activated cells of the immune system. Many of the CSS-associated cytokines mediate their downstream effects by signaling through the Janus kinases (JAKs) and signal transducers and activators of transcription (STATs). In addition, several of these cytokines are produced downstream of JAK/STAT pathway activation. Therefore, targeting JAK/STAT signaling using small molecule JAK inhibitors has become an increasingly appealing therapeutic option to dampen hyperinflammation in patients with CSSs. Application of JAK inhibitors in preclinical CSS models has shown improvements in multiple sequelae of hyperinflammation, and there is growing clinical evidence supporting the efficacy of JAK inhibition in patients with these conditions. Although generally well tolerated, JAK inhibitor use is not without potential for toxicity, especially in settings like CSSs where end-organ dysfunction is common. More prospective clinical trials incorporating JAK inhibitors, alone or in combination with other immunomodulatory therapies, are necessary to determine the optimal dosing, schedule, efficacy, and tolerability of these agents for patients experiencing CSSs.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quinasas Janus / Inhibidores de las Cinasas Janus / Síndrome de Liberación de Citoquinas Límite: Animals / Humans Idioma: En Revista: Adv Exp Med Biol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Quinasas Janus / Inhibidores de las Cinasas Janus / Síndrome de Liberación de Citoquinas Límite: Animals / Humans Idioma: En Revista: Adv Exp Med Biol Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos