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International Immunology, Vol. 15, No. 2, pp. 233-240, February 2003
© 2003 Japanese Society for Immunology

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

Isabelle Cloëz-Tayarani1, Anne-France Petit-Bertron1, Homer D. Venters2 and Jean-Marc Cavaillon1

1 UP Cytokines & Inflammation, Institut Pasteur, 25–28 rue du Dr Roux, 75015 Paris, France 2 165 Medical Sciences, 506 S. Mathews, Urbana, IL 61801, USA

Correspondence to: I. Cloëz-Tayarani; E-mail: icloez{at}pasteur.fr
Transmitting editor: T. Watanabe

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)-{alpha}, IL-1{alpha}, IL-1ß, IL-6, IL-10 and IL-1 receptor antagonist in lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMC). 5-HT inhibited TNF-{alpha} production and increased IL-1ß production in PBMC. The level of IL-1ß-converting enzyme/caspase-1 remained unchanged, suggesting that the effect of 5-HT is not directly related to the IL-1ß maturation process. TNF-{alpha} mRNA and IL-1ß 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-{alpha} 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-{alpha} 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.

Keywords: IL-1, inflammation, tumor necrosis factor


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