Evidence that cisplatin induces serotonin release from human peripheral blood mononuclear cells and that methylprednisolone inhibits this effect.
Corticosteroids counteract cisplatin (CDDP)-induced acute emesis but the mechanism involved is still unknown. Therefore, the aim of this study was to verify whether CDDP can induce serotonin (5HT) release from peripheral blood mononuclear cells (PBMC) and determine whether methylprednisolone (MP) can inhibit such release. Blood from 10 healthy volunteers was used. Our study showed that CDDP did induce 5HT release from PBMC dose-dependently (10 +/- 1 nM for controls, 18 +/- 4 nM for CDDP 0.01 microgram and 30 +/- 4 nM for CDDP 0.1 microgram, P < 0.001) and that the addition of MP to cultures of PBMC in the presence of CDDP induced a significant decrease of 5HT concentrations. Our results highlight a new mechanism through which CDDP could induce emesis and suggest a further mechanism by which corticosteroids mediate their anti-emetic effect.
Mantovani
G
G
Department of Medical Oncology, University of Cagliari, Italy.
Macciò
A
A
Esu
S
S
Lai
P
P
D000932:Antiemetics / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018929:Cell Culture Techniques; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000378:metabolism; D008776:Methylprednisolone Hemisuccinate / Q000494:pharmacology*; D012701:Serotonin / Q000097:blood*
D000932:Antiemetics; D000970:Antineoplastic Agents; D012701:Serotonin; D008776:Methylprednisolone Hemisuccinate; D002945:Cisplatin