Cis-platinum-induced immunosuppression: Relationship to melatonin in humanperipheral blood mononuclear cells

Objectives: The purpose of this study was to investigate the immunomodulato ry effect of melatonin (MLT) on human peripheral blood mononuclear cells (P BMC) and to address its effects on Cia-platinum (CDDP)-induced cytotoxicity . Methods and results: The obtained data from this study revealed that treatm ent of cells with MLT (100 mu g/ml) for 24 h enhanced cell viability. When cells were exposed to CDDP (5 mu g/ml), cell proliferation in response to p hytohaemagglutinin (PHA) stimulation was reduced by similar to 49.63% compa red to control cells as detected by (3)[H]-thymidine uptake. Furthermore, C is-platinum significantly depleted intracellular glutathione (GSH) levels b y similar to 47% below that of untreated cells and led to apoptotic changes in the target cells as evidenced by DNA fragmentation (45% compared to 5% in control cells as measured by diphenylamine assay). DNA fragmentation was also confirmed by agarose gel electrophoresis. However, MLT enhanced cell proliferation by similar to 8.63% above the control values, and counteracte d the antiproliferative effect of CDDP. The GSH levels' were significantly increased in response to MLT (71% above control values) and it protected th e cells against GSH depletion induced by CDDP. Moreover, DNA fragmentation and laddering produced by CDDP were significantly reduced or even disappear ed when the cells were pretreated with MLT or the latter was simultaneously added with CDDP. Conclusions: The findings from this study indicated that melatonin is a pot ent immunomodulatory hormone that protects PBMC against cis-platinum-induce d immunosuppressive effects. These effects might improve the patients' resp onse to cis-platinum therapy and, therefore, their survival rates. Copyrigh t (C) 1999 The Canadian Society of Clinical Chemists.