Adenosine: a mediator of interleukin-1 beta-induced hippocampal synaptic inhibition

Interleukin-1 (IL-1) is a pleotrophic cytokine implicated in a variety of c entral activities, including fever, sleep, ischemic injury, and neuromodula tory responses, such as neuroimmune, and neuroendocrine interactions. Altho ugh accumulating evidence is available regarding the expression pattern of this cytokine, its receptors in the CNS, and its mechanistic profile under pathological levels, it is unclear whether this substance modulates central neurons under physiological concentrations. Further, in light of the funct ional and spatial overlap between the adenosine and IL-1 systems, it is not known whether these two systems are coupled. We report here that, in rat b rain slices, brief application of sub-femtomolar IL-1 beta causes a profoun d decrease of glutamate transmission, but not GABAergic inhibition, in hipp ocampal CA1 pyramidal neurons. This decrease by IL-1 beta is prevented by p harmacological blockade of adenosine A(1) receptors. In addition, we show t hat IL-1 beta failed to suppress glutamate transmission at room temperature . Because the production and release of adenosine in the CNS is thought to be metabolically dependent, this observation suggests that one of the funct ions of IL-1 beta is to increase the endogenous production of adenosine. To gether, these data suggest for the first time that sub-femtomolar levels of IL-1 can effectively modulate glutamate excitation in hippocampal neurons via an adenosine-dependent mechanism.