Cis-platinum-induced immunosuppression: relationship to melatonin in human peripheral blood mononuclear cells.
OBJECTIVE
The purpose of this study was to investigate the immunomodulatory effect of melatonin (MLT) on human peripheral blood mononuclear cells (PBMC) and to address its effects on Cis-platinum (CDDP)-induced cytotoxicity.


RESULTS
The obtained data from this study revealed that treatment of cells with MLT (100 microg/ml) for 24 h enhanced cell viability. When cells were exposed to CDDP (5 microg/ml), cell proliferation in response to phytohaemagglutinin (PHA) stimulation was reduced by 49.63% compared to control cells as detected by 3[H]-thymidine uptake. Furthermore, Cis-platinum significantly depleted intracellular glutathione (GSH) levels by approximately 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 approximately 8.63% above the control values, and counteracted the antiproliferative effect of CDDP. The GSH levels were significantly increased in response to MLT (71% above control values) and it protected the cells against GSH depletion induced by CDDP. Moreover, DNA fragmentation and laddering produced by CDDP were significantly reduced or even disappeared 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 potent immunomodulatory hormone that protects PBMC against cis-platinum-induced immunosuppressive effects. These effects might improve the patients' response to cis-platinum therapy and, therefore, their survival rates.
Hassan
M I
MI
Biochemistry Department, Ain Shams Faculty of Medicine, Abassia, Cairo, Egypt.
Ahmed
M I
MI
Kassim
S K
SK
Rashad
A
A
Khalifa
A
A
D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival; D002478:Cells, Cultured; D002945:Cisplatin / Q000494:pharmacology*; D053938:DNA Fragmentation; D005978:Glutathione / Q000097:blood; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007700:Kinetics; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000502:physiology; D008550:Melatonin / Q000494:pharmacology*; D010835:Phytohemagglutinins
D000276:Adjuvants, Immunologic; D007166:Immunosuppressive Agents; D010835:Phytohemagglutinins; D005978:Glutathione; D008550:Melatonin; D002945:Cisplatin