Interleukin-1F7B (IL-1H4/IL-1F7) is processed by caspase-1 and mature IL-1F7B binds to the IL-18 receptor but does not induce IFN-gamma production

Cytokine. 2002 Apr 21;18(2):61-71. doi: 10.1006/cyto.2002.0873.


We have recently reported the identification of four novel members of the interleukin-1 (IL-1) family which we designated as IL-1 homologue 1-4 (IL-1H1-4). These proteins exhibit significant sequence homology to other members of the IL-1 family. Of these homologues, only IL-1H4 (renamed IL-1F7b) was predicted to contain a propeptide domain and a caspase cleavage site. We now report that caspase-1 cleaves IL-1F7b at the predicted site to generate mature IL-1F7b. Caspase-4 was also able to process IL-1F7b, albeit inefficiently. Other caspases and Granzyme-B did not cleave IL-1F7b. Furthermore, adenovirus-mediated expression of IL-1F7b in HEK 293 cells led to in situ processing and secretion of mature IL-1F7b. In a screen to identify a potential receptor, both pro and mature IL-1F7b bound to the soluble IL-18 receptor alpha-Fc (IL-18Ralpha-Fc) but not to the soluble IL-1R-Fc or ST2R-Fc fusion proteins. Mature IL-1F7b bound to the IL-18Ralpha-Fc protein with higher affinity than the pro form, although the affinities for both proteins were significantly lower than that observed for IL-18. Consistent with this observation, only IL-18 and not IL-1F7b induced IFN-gamma production by KG1a cells. We also report that pro and mature IL-1F7b form homodimers with association constants of 4 microM and 5 nM, respectively, suggesting biological relevance to IL-1F7b processing. Finally, we have localized the expression of IL-1F7b protein in discrete cell populations including plasma cells and tumor cells. These data suggest that IL-1F7b may be involved in immune response, inflammatory diseases and/or cancer.

MeSH terms

  • Amino Acid Sequence
  • Binding Sites
  • Caspase 1 / metabolism*
  • Caspases / metabolism*
  • Cell Line
  • DNA, Complementary
  • Humans
  • Interferon-gamma / biosynthesis*
  • Interleukin-1 / genetics*
  • Interleukin-1 / metabolism*
  • Interleukin-18 / metabolism*
  • Interleukin-18 Receptor alpha Subunit
  • Receptors, Interleukin / metabolism*
  • Receptors, Interleukin-18
  • Recombinant Fusion Proteins / metabolism


  • DNA, Complementary
  • IL18R1 protein, human
  • Interleukin-1
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • Receptors, Interleukin
  • Receptors, Interleukin-18
  • Recombinant Fusion Proteins
  • interleukin-1 homolog 4, human
  • Interferon-gamma
  • Caspases
  • Caspase 1