Central Origin of IL-1β Produced During Peripheral Inflammation: Role of Meninges

Summary

Modulation of IL-1β in the central nervous system is well documented. In the murine model of systemic inflammation induced by peripheral injection of lipopolysaccharide (LPS), data consensually demonstrated an increase of brain IL-1β mRNA after LPS treatment. Expression at the protein level has been much more widely debated, mainly in the cases of demonstrations assessed by methods using global extracts of brain tissues. We hypothesized that these discrepancies may originate from contaminations by meningial tissue. Indeed, meninges belong to the periphery and are highly responsive to LPS. We have evaluated the contribution of this tissue in the IL-1β response of hippocampus, cortex and cerebellum from mice treated with LPS or RPMI. Comparison of IL-1β mRNA levels in extracts from structures collected with meninges to structures cautiously stripped from meningial membranes, vessels and choroid plexus showed that two thirds of the signal had a meningial origin. The contribution of the brain parenchyma itself was likely overestimated, as meninges remained in the brain foldings despite a careful dissection. Immunohistochemical studies of IL-1β on brain sections corroborated these results: staining was only observed in a few large cells located in the membranes surrounding the whole brain. No obvious staining was found in the parenchyma, at least with the doses of LPS we used.

These results show that the meningial tissue can constitute the major source of contamination of nervous parenchyma IL- 1β by peripheral IL- 1β if meninges are not removed. They tempt to the greatest care when analyzing data obtained from global extracts of the brain.