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


Dr Fabian Docagne, 2Grupo de Neuroinmunologia, as above.


Most pathologies of the brain have an inflammatory component, associated with the release of cytokines such as interleukin-1β (IL-1β) 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-1β, IL-1RI and IL-1RII in distinct inflammatory lesions in the rat brain. IL-1β 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-1β synthesis 2 h after the intracerebral microinjection of IL-1β; this de novo IL-1β 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-1β 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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