Aim: 

The pleiotropic inflammatory cytokine interleukin 18 (IL-18) is an anorexigenic agent and a regulator of energy efficiency. In order to understand the sites and the mechanisms of action of IL-18 in the central nervous system (CNS), we characterized members of its family in the mouse brain and neuronal cells.

Methods: 

The functional IL-18 receptor complex (IL-18Ralfa and beta) was cloned in the CNS of C57B/6 mice in order to perform in situ hybridization. RT-PCR and Western blot assay were also performed on in vitro hypothalamic and immunitary cell lines.

Results: 

In situ hybridization showed an extensive expression of IL-18Rs in the cortex, the hippocampus, and the hypothalamus. In addition to the canonical IL-18Ralfa, a truncated variant of this receptor subunit was also detected. In vitro studies demonstrated that in hypothalamic neurons expressing IL-18 and IL-18Rs, the application of IL-18 inhibits ERK1/2, p38 and STAT3 and these effects are different from those occurring in cells of the immune system.

Conclusion: 

This study demonstrates for the first time that IL-18Rs are highly expressed in CNS, including in those areas involved in the food intake. The coupling of IL-18 to different signaling mechanisms may provide the molecular basis for its action at central level.