Peripheral origin of IL-1β production in the rodent hippocampus under in vivo systemic bacterial lipopolysaccharide (LPS) challenge and its regulation by P2X7 receptors

In this study we showed that in vivo bacterial lipopolysaccharide (LPS) challenge elevated IL-1 beta level in the rodent hippocampus. Antagonists of P2X receptors inhibited LPS-induced IL-1 beta level with a pharmacological profile similar to that of P2X(7)R and their inhibitory effect was attenuated in the absence of P2X7R. In wildtype mice, LPS overexpressed mRNA encoding P2X(4) and P2X(7) receptors in the hippocampus and caused also a remarkable increase in the levels of IL-1 beta in the serum. The hippocampal increase of IL-1 beta has substantially alleviated when contamination of circulating blood cells was excluded by transcardial perfusion, indicating the peripheral origin of hippocampal elevation. These results point to the key role of the endogenous activation of peripheral P2X7R in the level of IL-1 beta in rodent hippocampus under systemic bacterial endotoxin challenge (C) 2009 Elsevier B V. All rights reserved