Effect of Endotoxin and Interleukin‐1β on Corticotropin‐Releasing‐Factor and Prostaglandin Release by Rat Brainstem Slices

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Abstract
This study investigated the effects of lipopolysaccharide (LPS) and interleukin-1β (IL-1β) on corticotropin releasing factor (CRF) and prostaglandin E2 (PGE2) release by brainstem slices in vitro. First, we characterized our experimental model and demonstrated that high potassium stimulates CRF release from rat brainstem slices in a calcium dependent way. The direct stimulation of brainstem slices with IL-1β (3–25 pM) did not modify basal or potassium-stimulated CRF release, although IL-1β at the dose of 25 pM increased PGE2 production. Peripheral injection (ip) of LPS (1–10 μg/kg) or IL-1β (1–10 μg/kg) evoked a dose-related potentiation of the ex-vivo release of CRF and PGE2 from brainstem slices. However, central (icv) administration of LPS (10–500 ng/rat) potentiated the release of CRF and PGE2 only at the dose of 500 ng/rat, whereas IL-1β (1–100 ng/rat) failed to modify significantly the ex vivo production of both CRF and PGE2. The results of the present study provide evidence that peripheral, rather than central, endotoxin and IL-1β administration induce the activation of brainstem CRF and PGE2, supporting the hypothesis that peripheral cytokine signalling to the CNS is mediated by stimulation of peripheral afferents.