The molecular evolution of the interleukin-1 family of cytokines; IL-18 in teleost fish

Dev Comp Immunol. 2004 May 3;28(5):395-413. doi: 10.1016/j.dci.2003.09.005.


The cytokine network is an important homeostatic system with potent activities in immune surveillance, growth, developmental and repair processes. Although interleukin-1beta (IL-1beta) is considered a pivotal pro-inflammatory cytokine, merely focussing on its inflammatory role would be too narrow an approach. Elucidation of the human, the mouse and the Fugu rubripes (pufferfish) genome now enables a more comprehensive overview of this cytokine family and its receptors in several vertebrate classes. Phylogenetic analyses of the IL-1 family members, comprising over 80 sequences of various fish, amphibian, avian and mammalian species, reveal that for only a few mammalian IL-1 family members unambiguous orthologues have been found in fish, indicating a recent origin of some of the mammalian IL-1 family members. Interestingly, the Fugu genome did reveal teleost orthologues for IL-18 and its putative receptor complex. All teleost IL-1beta sequences cluster separately from IL-1beta sequences of other species. In contrast, a number of IL-1 receptor family members have well conserved fish orthologues. This supports the concept of an ancestral role of this family, possibly in the brain.

Publication types

  • Review

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Caspases / genetics
  • Conserved Sequence
  • Evolution, Molecular*
  • Humans
  • Interleukin-1 / genetics*
  • Interleukin-18 / genetics*
  • Interleukin-18 Receptor alpha Subunit
  • Invertebrates / genetics
  • Invertebrates / immunology
  • Ligands
  • Molecular Sequence Data
  • Multigene Family
  • Phylogeny
  • Polymorphism, Genetic
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin-1 / genetics
  • Receptors, Interleukin-18
  • Sequence Homology, Amino Acid
  • Takifugu / genetics*
  • Takifugu / immunology*
  • Zebrafish / genetics
  • Zebrafish / immunology


  • IL18R1 protein, human
  • Il18r1 protein, mouse
  • Interleukin-1
  • Interleukin-18
  • Interleukin-18 Receptor alpha Subunit
  • Ligands
  • Receptors, Interleukin
  • Receptors, Interleukin-1
  • Receptors, Interleukin-18
  • Caspases