IL-18 and IL-33 elicit Th2 cytokines from basophils via a MyD88- and p38alpha-dependent pathway

J Leukoc Biol. 2009 Oct;86(4):769-78. doi: 10.1189/jlb.0708452. Epub 2009 May 18.


IL-4 and IL-13 are instrumental in the development and progression of allergy and atopic disease. Basophils represent a key source of these cytokines and produce IL-4 and IL-13 when stimulated with IL-18, a member of the IL-1 family of cytokines. Comparative analyses of the effects of caspase-1-dependent IL-1 family cytokines on basophil IL-4 and IL-13 production have not been performed, and the signaling pathway proteins required for FcepsilonRI-independent Th2 cytokine production from basophils remain incompletely defined. Using mouse bone marrow-derived cultured basophils, we found that IL-4 and IL-13 are produced in response to IL-18 or IL-33 stimulation. IL-18- or IL-33-mediated Th2 cytokine production is dependent on MyD88 and p38alpha signaling proteins. In addition, basophil survival increased in the presence of IL-18 or IL-33 as a result of increased Akt activation. Studies in vivo confirmed the potency of IL-18 and IL-33 in activating cytokine release from mouse basophils.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Basophils / cytology
  • Basophils / immunology*
  • Cell Survival / drug effects
  • Cell Survival / immunology
  • Cells, Cultured
  • Female
  • Interleukin-13 / immunology
  • Interleukin-18 / immunology
  • Interleukin-18 / pharmacology*
  • Interleukin-33
  • Interleukin-4 / immunology
  • Interleukins / immunology
  • Interleukins / pharmacology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Knockout
  • Mitogen-Activated Protein Kinase 14 / immunology*
  • Myeloid Differentiation Factor 88 / immunology*
  • Proto-Oncogene Proteins c-akt / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology*
  • Th2 Cells / immunology*


  • Il33 protein, mouse
  • Interleukin-13
  • Interleukin-18
  • Interleukin-33
  • Interleukins
  • Myd88 protein, mouse
  • Myeloid Differentiation Factor 88
  • Interleukin-4
  • Proto-Oncogene Proteins c-akt
  • Mitogen-Activated Protein Kinase 14