Antiinflammatory effects of 5-HT3 receptor antagonists in lipopolysaccharide-stimulated primary human monocytes.
There is evidence from both human and animal research that 5-hydroxytryptamine (5-HT)3 receptor antagonists, particularly tropisetron, exert analgesic and antiinflammatory effects. However, the underlying mechanisms of these effects have not yet been investigated in detail. Therefore, the antiinflammatory effects of tropisetron and ondansetron were investigated in human monocytes. In human monocytes, both lipopolysaccharide (LPS)-stimulated tumour necrosis factor (TNF)-alpha and interleukin (IL)-1beta secretion were dose-dependently inhibited by tropisetron starting at a concentration of 5 microg/mL and reaching maximal levels at 25 microg/mL (IC50: 32 microg/mL and 12 microg/mL, respectively). LPS-induced IL-6 and PGE2 release was only slightly inhibited at high doses, whereas LPS-induced release of IL-8 and matrix metalloprotease (MMP)-9 was not affected. In conclusion, our data show that the binding of tropisetron to 5-HT3 receptors results in antiinflammatory effects through inhibition of TNF-alpha/IL-1beta, which might explain the antiphlogistic effects of 5-HT3 antagonists.
Fiebich
B L
BL
Department of Psychiatry and Psychotherapy, University of Freiburg Medical School, Germany. bernd.fiebich@klinikum.uni-freiburg.de
Akundi
R S
RS
Lieb
K
K
Candelario-Jalil
E
E
Gmeiner
D
D
Haus
U
U
Müller
W
W
Stratz
T
T
Muñoz
E
E
D002478:Cells, Cultured; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology*; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists / Q000627:therapeutic use*; D000077526:Tropisetron
D007211:Indoles; D008070:Lipopolysaccharides; D058831:Serotonin 5-HT3 Receptor Antagonists; D012702:Serotonin Antagonists; D000077526:Tropisetron