In vitro effects of platinum compounds on lymphocyte proliferation and cytokine release.
In vitro immune effects of Pt compounds of occupational and/or environmental importance, or those used in cancer treatment were studied. Spontaneous and PHA-stimulated proliferation of peripheral blood mononuclear cells (PBMC) and in vitro release of TNF-alpha, IFN-gamma, and IL-5 were assessed in presence of high and very low concentrations of Pt salts: 10(-4) and 10(-7) M (NH4)2[PtCl6], (NH4)2[PtCl4], PtCl4, PtCl2, Na2PtI6, and cis-diaminedichloroPt (CisPt). Spontaneous and PHA-stimulated PBMC proliferation were both inhibited by 10(-4) M (NH4)2[PtCl6] and (NH4)2[PtCl4], while only PHA-stimulated proliferation was inhibited by 10(-4) M CisPt, without significant effects of the other Pt salts. TNF-alpha release from PBMC was reduced by 10(-4) M (NH4)2[PtCl6] and INF-gamma release was reduced by 10(-4) and 10(-7) M hexa- and tetrachloroplatinate and 10(-4) M Na2PtI6, but not by other Pt salts. IL-5 release (related to the Th2 immune response) was inhibited by 10(-4) M (NH4)2[PtCl6], (NH4)2[PtCl4] and Na2PtI6, but it was enhanced by both 10(-4) and 10(-7) M PtCl4. PtCl2 did not influence the immune effects. The study shows Pt salts have immune effects and their potency is ranked in the following order: (NH4)2[PtCl6] > (NH4)2[PtCl4] > Na2PtI6 and CisPt > PtCl4 > PtCl2. These results indicate that certain Pt salts affect lymphocyte proliferation and cytokine release. The intracellular mechanisms responsible for such effects have not been identified.
Di Gioacchino
Mario
M
Department of Medicine and Science of Ageing, G. D'Annunzio University of Chieti, Italy. m.digioacchino@unich.it
Di Giampaolo
Luca
L
Verna
Nicola
N
Reale
Marcella
M
Di Sciascio
Maria Bernadette
MB
Volpe
Anna Rita
AR
Carmignani
Marco
M
Ponti
Jessica
J
Paganelli
Roberto
R
Sabbioni
Enrico
E
Boscolo
Paolo
P
D000328:Adult; D016207:Cytokines / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D015848:Interleukin-5 / Q000096:biosynthesis; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000166:cytology / Q000276:immunology; D008297:Male; D008875:Middle Aged; D017671:Platinum Compounds / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D016207:Cytokines; D015848:Interleukin-5; D017671:Platinum Compounds; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma