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-1β level in the rodent hippocampus. Antagonists of P2X receptors inhibited LPS-induced IL-1β level with a pharmacological profile similar to that of P2X7R and their inhibitory effect was attenuated in the absence of P2X7R. In wild-type mice, LPS overexpressed mRNA encoding P2X4 and P2X7 receptors in the hippocampus and caused also a remarkable increase in the levels of IL-1β in the serum. The hippocampal increase of IL-1β has substantially alleviated when contamination of circulating blood cells was excluded by transcardial perfusion, indicating the peripheral origin of hippocampal IL-1β elevation. These results point to the key role of the endogenous activation of peripheral P2X7R in the level of IL-1β in rodent hippocampus under systemic bacterial endotoxin challenge.