IL-1 Family Blockade in Cytokine Storm Syndromes

Adv Exp Med Biol. 2024:1448:553-563. doi: 10.1007/978-3-031-59815-9_36.

Abstract

Interleukin-1 is a prototypic proinflammatory cytokine that is elevated in cytokine storm syndromes (CSSs), such as secondary hemophagocytic lymphohistiocytosis (sHLH) and macrophage activation syndrome (MAS). IL-1 has many pleotropic and redundant roles in both innate and adaptive immune responses. Blockade of IL-1 with recombinant human interleukin-1 receptor antagonist has shown efficacy in treating CSS. Recently, an IL-1 family member, IL-18, has been demonstrated to be contributory to CSS in autoinflammatory conditions, such as in inflammasomopathies (e.g., NLRC4 mutations). Anecdotally, recombinant IL-18 binding protein can be of benefit in treating IL-18-driven CSS. Lastly, another IL-1 family member, IL-33, has been postulated to contribute to CSS in an animal model of disease. Targeting of IL-1 and related cytokines holds promise in treating a variety of CSS.

Keywords: Anakinra; Cytokine storm syndrome; IL-1 receptor antagonist; IL-18 binding protein; Interleukin-1 (IL-1); Interleukin-1 receptor-like 1; Interleukin-18 (IL-18); Interleukin-33 (IL-33); Macrophage activation syndrome; Secondary hemophagocytic lymphohistiocytosis.

Publication types

  • Review

MeSH terms

  • Animals
  • CARD Signaling Adaptor Proteins
  • Calcium-Binding Proteins / genetics
  • Cytokine Release Syndrome* / drug therapy
  • Cytokine Release Syndrome* / immunology
  • Humans
  • Interleukin 1 Receptor Antagonist Protein / genetics
  • Interleukin 1 Receptor Antagonist Protein / therapeutic use
  • Interleukin-1* / antagonists & inhibitors
  • Interleukin-1* / genetics
  • Interleukin-1* / immunology
  • Interleukin-1* / metabolism
  • Interleukin-18 / genetics
  • Interleukin-18 / immunology
  • Lymphohistiocytosis, Hemophagocytic / drug therapy
  • Lymphohistiocytosis, Hemophagocytic / genetics
  • Lymphohistiocytosis, Hemophagocytic / immunology
  • Macrophage Activation Syndrome / drug therapy
  • Macrophage Activation Syndrome / genetics
  • Macrophage Activation Syndrome / immunology

Substances

  • Interleukin-1
  • Interleukin 1 Receptor Antagonist Protein
  • Calcium-Binding Proteins
  • Interleukin-18
  • NLRC4 protein, human
  • CARD Signaling Adaptor Proteins