The ST2/Interleukin-33 Axis in Hematologic Malignancies: The IL-33 Paradox

Int J Mol Sci. 2019 Oct 22;20(20):5226. doi: 10.3390/ijms20205226.


Interleukin (IL)-33 is a chromatin-related nuclear interleukin that is a component of IL-1 family. IL-33 production augments the course of inflammation after cell damage or death. It is discharged into the extracellular space. IL-33 is regarded as an "alarmin" able to stimulate several effectors of the immune system, regulating numerous immune responses comprising cancer immune reactions. IL-33 has been demonstrated to influence tumorigenesis. However, as far as this cytokine is concerned, we are faced with what has sometimes been defined as the IL-33 paradox. Several studies have demonstrated a relevant role of IL-33 to numerous malignancies, where it may have pro- and-less frequently-antitumorigenic actions. In the field of hematological malignancies, the role of IL-33 seems even more complex. Although we can affirm the existence of a negative role of IL-33 in Chronic myelogenos leukemia (CML) and in lymphoproliferative diseases and a positive role in pathologies such as Acute myeloid leukemia (AML), the action of IL-33 seems to be multiple and sometimes contradictory within the same pathology. In the future, we will have to learn to govern the negative aspects of activating the IL-33/ST2 axis and exploit the positive ones.

Keywords: alarmin; hematologic malignancies; immune response; interleukin 33; tumorigenesis.

Publication types

  • Review

MeSH terms

  • Animals
  • Hematologic Neoplasms / genetics
  • Hematologic Neoplasms / metabolism*
  • Humans
  • Interleukin-1 Receptor-Like 1 Protein / genetics
  • Interleukin-1 Receptor-Like 1 Protein / metabolism*
  • Interleukin-33 / genetics
  • Interleukin-33 / metabolism*
  • Signal Transduction


  • Interleukin-1 Receptor-Like 1 Protein
  • Interleukin-33