Inhibition of interleukin-1β reduces myelofibrosis and osteosclerosis in mice with JAK2-V617F driven myeloproliferative neoplasm

Nat Commun. 2022 Sep 13;13(1):5346. doi: 10.1038/s41467-022-32927-4.


Interleukin-1β (IL-1β) is a master regulator of inflammation. Increased activity of IL-1β has been implicated in various pathological conditions including myeloproliferative neoplasms (MPNs). Here we show that IL-1β serum levels and expression of IL-1 receptors on hematopoietic progenitors and stem cells correlate with JAK2-V617F mutant allele fraction in peripheral blood of patients with MPN. We show that the source of IL-1β overproduction in a mouse model of MPN are JAK2-V617F expressing hematopoietic cells. Knockout of IL-1β in hematopoietic cells of JAK2-V617F mice reduces inflammatory cytokines, prevents damage to nestin-positive niche cells and reduces megakaryopoiesis, resulting in decrease of myelofibrosis and osteosclerosis. Inhibition of IL-1β in JAK2-V617F mutant mice by anti-IL-1β antibody also reduces myelofibrosis and osteosclerosis and shows additive effects with ruxolitinib. These results suggest that inhibition of IL-1β with anti-IL-1β antibody alone or in combination with ruxolitinib could have beneficial effects on the clinical course in patients with myelofibrosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Interleukin-1beta / metabolism*
  • Janus Kinase 2 / genetics*
  • Janus Kinase 2 / metabolism
  • Mice
  • Mice, Knockout
  • Myeloproliferative Disorders* / drug therapy
  • Myeloproliferative Disorders* / genetics
  • Myeloproliferative Disorders* / metabolism
  • Neoplasms*
  • Nitriles
  • Osteosclerosis* / genetics
  • Primary Myelofibrosis* / drug therapy
  • Primary Myelofibrosis* / genetics
  • Pyrazoles
  • Pyrimidines


  • IL1B protein, mouse
  • Interleukin-1beta
  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib
  • Jak2 protein, mouse
  • Janus Kinase 2