Cisplatin-based polychemotherapy reduces the natural cytotoxicity of peripheral blood mononuclear cells in patients with advanced ovarian carcinoma and their in vitro responsiveness to interleukin-12 incubation.
BACKGROUND
The aim of the current study was to evaluate the in vitro effect of IL-12 on the natural cytotoxicity of peripheral blood mononuclear cells (PBMCs) obtained from patients who underwent adjuvant-based cisplatin polychemotherapy for advanced ovarian carcinoma. The authors also investigated amifostine, a cytoprotective agent that appears to protect against chemotherapy damage to healthy tissues, to determine its effects on natural immune function.


METHODS
Twenty-one women with advanced ovarian serous cystoadenocarcinoma who underwent adjuvant cisplatin-based polychemotherapy were included in the study, and 20 normal volunteer women matched for age served as controls. Six of the 21 women who underwent polychemotherapy received 1:3 amifostine pretreatment. Blood samples were obtained immediately before the first cycle of cisplatin-based polychemotherapy and within 24 hours after the completion of polychemotherapy infusion to evaluate the natural cytotoxic activity of PBMCs against the K562 cell line and the in vitro responsiveness of cytotoxic cells to interleukin-12 (IL-12).


RESULTS
The in vivo administration of cisplatin-based polychemotherapy significantly reduced the natural killer cytotoxicity of PBMCs toward undetectable levels (2.2+/-3.1 vs. 9.2+/-7.0 lytic units, respectively, after and before cisplatin; P < 0.01), and the in vitro exposure to IL-12 did not increase the cytolytic activity of PBMCs (1.9+/-2.1 lytic units). PBMCs from the 6 patients who received random amifostine pretreatment were shown to have retained natural killer cytotoxicity after in vivo administration of cisplatin polychemotherapy (9.7+/-6.7 vs. 9.6+/-6.0 lytic units, respectively, after and before cisplatin; P = 0.9), and the incubation with IL-12 increased cytotoxic activity (13.4+/-6.9 lytic units) toward the levels observed in PBMCs of controls (14.0+/-4.6 lytic units).


CONCLUSIONS
These data suggest that cisplatin-based polychemotherapy reduces the natural cytotoxicity of PBMCs in patients with advanced ovarian carcinoma as well as their in vitro responsiveness to IL-12 incubation. Amifostine demonstrated a protective effect on natural killer cell cytotoxicity and responsiveness to IL-12 in this small cohort of patients.
D004999:Amifostine / Q000008:administration & dosage / Q000494:pharmacology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage* / Q000494:pharmacology; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy* / Q000276:immunology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005260:Female; D006801:Humans; D007121:Immunocompetence / Q000187:drug effects; D066298:In Vitro Techniques; D018664:Interleukin-12 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects / Q000502:physiology*; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology; D011237:Predictive Value of Tests; D011379:Prognosis; D011837:Radiation-Protective Agents / Q000008:administration & dosage / Q000494:pharmacology