Differential regulation of type I and type II interleukin-1 receptors in focal brain inflammation

Docagne, F., Campbell, S.J., Bristow, A.F., Poole, S., Vigues, S., Guaza, C., Perry, V.H. and Anthony, D.C. (2005) Differential regulation of type I and type II interleukin-1 receptors in focal brain inflammation. European Journal of Neuroscience, 21 (5), 1205-1214. (doi:10.1111/j.1460-9568.2005.03965.x).

Abstract

Most pathologies of the brain have an inflammatory component, associated with the release of cytokines such as interleukin-1? (IL-1?) from resident and infiltrating cells. The IL-1 type I receptor (IL-1RI) initiates a signalling cascade but the type II receptor (IL-1RII) acts as a decoy receptor. Here we have investigated the expression of IL-1?, IL-1RI and IL-1RII in distinct inflammatory lesions in the rat brain. IL-1? was injected into the brain to generate an inflammatory lesion in the absence of neuronal cell death whereas neuronal death was specifically induced by the microinjection of N-methyl-d-aspartate (NMDA). Using TaqMan RT-PCR and ELISA, we observed elevated de novo IL-1? synthesis 2 h after the intracerebral microinjection of IL-1?; this de novo IL-1? remained elevated 24 h later. There was a concomitant increase in IL-1RI mRNA but a much greater increase in IL-1RII mRNA. Immunostaining revealed that IL-1RII was expressed on brain endothelial cells and on infiltrating neutrophils. In contrast, although IL-1? and IL-1RI were elevated to similar levels in response to NMDA challenge, the response was delayed and IL-1RII mRNA expression was unchanged. The lesion-specific expression of IL-1 receptors suggests that the receptors are differentially regulated in a manner not directly related to the endogenous level of IL-1 in the CNS.

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