Binding of interleukin-18 to the interleukin-1 receptor homologous receptor IL-1Rrp1 leads to activation of signaling pathways similar to those used by interleukin-1

J Interferon Cytokine Res. 1998 Dec;18(12):1077-88. doi: 10.1089/jir.1998.18.1077.


Interleukin-18 (IL-18) is an inflammatory cytokine that has been shown to enhance a variety of Th1 type T cell responses. Because IL-18 is homologous to IL-1, we tested binding of IL-18 to the known IL-1R family members. We could show binding of IL-18 to the orphan receptor IL-1Rrp1 but not to other IL-1R homologous proteins. IL-1Rrp1 and IL-1RI share highly conserved domains within their cytoplasmic regions. Comparison of the IL-1 and IL-18 signaling mechanisms showed that they activate identical cytoplasmic messengers. IL-18, like IL-1, induced association of its receptor with IRAK and subsequent recruitment of TRAF6. IL-18 activated p38 MAP kinase, jun kinase, and beta casein kinase (TIP kinase), an apparently novel kinase previously thought to be specifically activated by IL-1 and tumor necrosis factor (TNF). IL-18 activated NF-kappaB in EL4/6.1 thymoma cells but not in COS-7 cells, even though the latter presumably contain all components required for the IL-1 signaling pathway. From our binding and signaling studies, we conclude that the IL-18 receptor complex consists of IL-18, the IL-1Rrp1, and another thus far unidentified receptor molecule.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Calcium-Calmodulin-Dependent Protein Kinases / metabolism
  • Casein Kinases*
  • Cell Line
  • Enzyme Activation
  • Humans
  • Interleukin-1 / metabolism*
  • Interleukin-18 / metabolism*
  • Mice
  • NF-kappa B / metabolism
  • Precipitin Tests
  • Protein Kinases / metabolism
  • Receptors, Interleukin-1 / metabolism*
  • Signal Transduction / physiology*


  • Interleukin-1
  • Interleukin-18
  • NF-kappa B
  • Receptors, Interleukin-1
  • Protein Kinases
  • Casein Kinases
  • TNF-IL1-activated protein kinase
  • Calcium-Calmodulin-Dependent Protein Kinases