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 th e mechanism involved is still unknown. Therefore, the aim of this stud y was to verify whether CDDP can induce serotonin (5HT) release from p eripheral blood mononuclear cells (PBMC) and determine whether methylp rednisolone (MP) can inhibit such release. Blood from 10 healthy volun teers 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 mu g and 30 +/- 4 nM for CDDP 0.1 mu g, P < 0.001) and that the addition of MP to cultures of PBMC in the presence of CDDP induced a s ignificant decrease of 5HT concentrations. Our results highlight a new mechanism through which CDDP could induce emesis and suggest a furthe r mechanism by which corticosteroids mediate their anti-emetic effect. Copyright (C) 1996 Elsevier Science Ltd