Research ReportAnti-inflammatory substances can influence some glial cell types but not others

- Anti-inflammatory substances in ultralow concentrations affect glial cells.
- LPS treatment increases TNF-α and IL-1β release in microglia.
- Glucocorticoids attenuate cytokine release.
- Naloxone in ultralow concentrations increases TNF-α release.
- Ouabain in ultralow concentrations increases TNF-α release.

In rat microglial enriched cultures, expressing Toll-like receptor 4, we studied cytokine release after exposure with 1 ng/ml LPS for 0.5-24 h. Dexamethasone and corticosterone exposure served as controls. We focused on whether naloxone, ouabain, and bupivacaine, all agents with reported anti-inflammatory effects on astrocytes, could affect the release of TNF-α and IL-1β in microglia. Our results show that neither ultralow (10−12 M) nor high (10−6 M) concentrations of these agents had demonstrable effects on cytokine release in microglia. The results indicate that anti-inflammatory substances exert specific influences on different glial cell types. Astrocytes seem to be functional targets for anti-inflammatory substances while microglia respond directly to inflammatory stimuli and are thus more sensitive to anti-inflammatory substances like corticoids. The physiological relevance might be that astrocyte dysfunction influences neuronal signalling both due to direct disturbance of astrocyte functions and in the communication within the astrocyte networks. When the signalling between astrocytes is working, then microglia produce less pro-inflammatory cytokines.