title: Macrophage activation syndrome and cytokine-directed therapies.
abstract: Macrophage activation syndrome (MAS) is an episode of overwhelming inflammation that occurs most commonly in children with systemic juvenile idiopathic arthritis (SJIA). It is characterized by expansion and activation of T lymphocytes and hemophagocytic macrophages and bears great similarity to hemophagocytic lymphohistiocytosis (HLH). This disorder has substantial morbidity and mortality, and there is frequently a delay in recognition and initiation of treatment. Here, we will review what is known about the pathogenesis of MAS and, in particular, its similarities to HLH. The development of MAS is characterized by a cytokine storm, with the elaboration of numerous pro-inflammatory cytokines. We will examine the evidence for various cytokines in the initiation and pathogenesis of MAS and discuss how new biologic therapies may alter the risk of MAS. Finally, we will review current treatment options for MAS and examine how cytokine-directed therapy could serve as novel treatment modalities.
authors: Division of Pediatric Rheumatology, Children's Hospital Medical Center, MLC 4010, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. Electronic address: Grant.schulert@cchmc.org.
authors: Grant S
authors: GS
authors: Schulert
authors: Division of Pediatric Rheumatology, Children's Hospital Medical Center, MLC 4010, 3333 Burnet Avenue, Cincinnati, OH 45229, USA. Electronic address: Alexi.grom@cchmc.org.
authors: Alexei A
authors: AA
authors: Grom
mesh_terms: D000818:Animals; D001171:Arthritis, Juvenile / Q000188:drug therapy / Q000276:immunology*; D001685:Biological Factors / Q000627:therapeutic use; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000502:physiology*; D004195:Disease Models, Animal; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D051359:Lymphohistiocytosis, Hemophagocytic / Q000209:etiology; D055501:Macrophage Activation Syndrome / Q000188:drug therapy / Q000276:immunology*; D013601:T-Lymphocytes / Q000502:physiology; D000093242:Interleukin-6 Inhibitors
chemical_list: D001685:Biological Factors; D016207:Cytokines; D007375:Interleukin-1; D000093242:Interleukin-6 Inhibitors
keywords: Hemophagocytic lymphohistiocytosis; IFNγ; IL-1; IL-18; IL-6; Macrophage activation syndrome; Still's disease; Systemic juvenile idiopathic arthritis