Differential effect of serotonin on cytokine production in lipopolysaccharide‐stimulated human peripheral blood mononuclear cells: involvement of 5‐hydroxytryptamine2A receptors

In order to provide additional insight into the in vivo significance of serotonin [5‐hydroxytryptamine (5‐HT)] in inflammation, we examined its effect on the production of tumor necrosis factor (TNF)‐α, IL‐1α, IL‐1β, IL‐6, IL‐10 and IL‐1 receptor antagonist in lipopolysaccharide (LPS)‐stimulated human peripheral blood mononuclear cells (PBMC). 5‐HT inhibited TNF‐α production and increased IL‐1β production in PBMC. The level of IL‐1β‐converting enzyme/caspase‐1 remained unchanged, suggesting that the effect of 5‐HT is not directly related to the IL‐1β maturation process. TNF‐α mRNA and IL‐1β mRNA content did not change in the presence of 5‐HT. 5‐HT did not have any effect on the production of other cytokines studied. The inhibitory effect of 5‐HT on TNF‐α production was antagonized by ketanserin, a selective 5‐HT2A antagonist, and mimicked by DOI, a selective 5‐HT2A/2C agonist. These findings suggest that the inhibition of TNF‐α production by 5‐HT involves the participation of the 5‐HT2A receptor subtypes in PBMC. Accordingly, we detected the presence of 5‐HT2A receptors in PBMC by Western blot analysis. Our data support a role of 5‐HT in inflammation through its effect on cytokine production in PBMC.