Role of human blood monocytes in up-regulation of lymphokine (interleukin-2)-activated killer cell activity with cisplatin and FK-565.
The role of cisplatin (CP) and FK-565 in monocyte-mediated up-regulation of lymphokine-activated killer (LAK) cell induction by interleukin-2 (IL-2) was examined. Treatment of peripheral-blood mononuclear cells (PBMC) with CP or FK-565 in the presence of IL-2 resulted in a significant increase in LAK activity against NK-resistant Raji cells, as assessed by the 4-hour 51Cr release assay, depending on the dose of CP, FK-565 and IL-2. Up-regulation of IL-2-induced LAK activity by CP/FK-565 was significantly higher in whole PBMC as compared to PBMC depleted of monocytes. Addition of different numbers of monocytes to cultures of lymphocytes plus IL-2 along with CP or FK-565 resulted in a significant up-regulation of LAK activity depending on the number of monocytes added. Pretreatment of monocytes for 2 h with CP or FK-565 before addition of lymphocytes plus IL-2 resulted in significant up-regulation of LAK activity as compared to untreated monocytes. Culture supernatant of CP- or FK-565-treated monocytes also significantly up-regulated IL-2-induced LAK activity of lymphocytes. The results of the present investigation suggest that up-regulation of LAK activity by CP and FK-565 in human PBMC is monocyte-mediated. Further, our data demonstrate that tumor necrosis factor and IL-1 play an important role in the up-regulation of LAK activity by monocytes that have been pretreated with FK-565 or CP. These results indicate that CP and FK-565 may be useful in modulating the immune response during treatment of neoplasia with IL-2 and LAK therapies.
Sodhi
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School of Biotechnology, Banaras Hindu University, Varanasi, India.
Basu
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D000276:Adjuvants, Immunologic / Q000494:pharmacology; D002945:Cisplatin / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects* / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology; D009842:Oligopeptides / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000276:immunology; D015854:Up-Regulation / Q000187:drug effects
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D009842:Oligopeptides; C039537:heptanoyl-gamma-D-glutamyl-L-meso-diaminopimelyl-D-alanine; D002945:Cisplatin