Histamine inhibits IL-1β release induced by LPS administration in N9
microglial cells (a) and in hippocampal organotypic slice cultures (b)
measured by ELISA. (a) N9 microglial cells, upon inflammatory
challenge induced by LPS (100 ng/ml), are able to release a significantly
higher amount of proinflammatory cytokine IL-1β when compared to untreated
cells. Histamine treatment (100 μM) significantly inhibited this effect
through the activation of H4R. Accordingly, histamine-loaded
microparticles (μP 10 μg/ml) mimicked the anti-inflammatory effect of
histamine (left graph). The anti-inflammatory action of histamine
appears to modulate specifically the IL-1β signaling pathway, since it
does not alter the release of another relevant proinflammatory cytokine, such
as TNF-α, in the presence of 100 ng/ml LPS. Additionally, the application
of histamine-loaded microparticles (10 μg/ml) did not inhibit LPS-induced
TNF-α release (right graph). (b) Regarding hippocampal
organotypic slice cultures, only soluble histamine significantly decreased
IL-1β release induced by LPS. Again, H4R activation also
mimicked the effect of histamine, whereas H4R blockade partially
recuperated LPS-induced IL-1β release (right graph). Data are
expressed as mean ± SEM (n = 3-11),
(*p < 0.05, **p < 0.01,
***p < 0.001, using Bonferroni’s multiple
comparison test).