IL-1F5 mediates anti-inflammatory activity in the brain through induction of IL-4 following interaction with SIGIRR/TIR8

Ceire Costelloe, Melanie Watson, Aine Murphy, Keith McQuillan, Christine Loscher, Michelle E. Armstrong, Cecilia Garlanda, Alberto Mantovani, Luke A J O'Neill, Kingston H G Mills, Marina A. Lynch

Research output: Contribution to journalArticlepeer-review


Similarity in structure and sequence homology has led to the identification of new members of the interleukin-1 (IL-1) ligand and receptor superfamilies. IL-1F6, IL-1F8 and IL-1F9 have been shown to signal through IL-1R-related protein 2 and IL-1 receptor accessory protein leading to activation of NFκB, while IL-1F7 and IL-1F10 interact with the IL-18 receptor and the soluble IL-1 receptor type I respectively. In contrast, identification of a biological role for IL-1F5 has remained elusive, with conflicting data relating to its possible ability to antagonize IL-1F9-stimulated activation of NFκB in Jurkat cells transfected with IL-1R-related protein 2. In this study, we set out to investigate a possible role for IL-1F5 in the brain and report that it antagonizes the inflammatory effects of IL-1β and lipopolysaccharide (LPS) in vivo and in vitro including the inhibitory effect on long-term potentiation (LTP) in rat hippocampus. We demonstrate that IL-1F5 induces IL-4 mRNA and protein expression in glia in vitro and enhances hippocampal expression of IL-4 following intracerebroventricular (i.c.v.) injection. The inhibitory effect of IL-1F5 on LPS-induced IL-1β is attenuated in cells from IL-4-defective (IL-4-/- mice). Our findings suggest that IL-1F5 mediates anti-inflammatory effects through its ability to induce IL-4 production and that this is a consequence of its interaction with the orphan receptor, single Ig IL-1R-related molecule (SIGIRR)/TIR8, as the effects were not observed in SIGIRR-/- mice. In contrast to its effects in brain tissue, IL-1F5 did not attenuate LPS-induced changes, or up-regulated IL-4 in macrophages or dendritic cells, suggesting that the effect is confined to the brain.

Original languageEnglish
Pages (from-to)1960-1969
Number of pages10
JournalJournal of Neurochemistry
Issue number5
Publication statusPublished - Jun 2008


  • Cytokine
  • Cytokine receptor
  • Interleukin-1β
  • Interleukin-4
  • Single Ig IL-1 receptor-related molecule

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience


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