Effects of cryopreservation on immune responses. X. Decrease in interleukin-12 production by frozen human peripheral blood mononuclear cells is mediated by the endogenously hypersecreted interleukin-10.
The contrasting effects of freezing and radiation on lipopolysaccharide (LPS)-induced interleukin (IL)-10 production by human peripheral blood mononuclear cells (PBMCs) have recently been reported. In view of the potent inhibitory properties of IL-10 on IL-12 secretion and the central role played by IL-12 in the immune system, the influences of freezing and radiation on LPS-induced IL-12 production by PBMCs were studied. Frozen PBMCs secreted significantly smaller amounts of IL-12 than fresh cells. In contrast, the in vitro-irradiated PBMCs produced significantly larger amounts of IL-12. Culture of frozen cells in the presence of exogenous anti-IL-10 antibody resulted in the production of significantly larger amounts of IL-12. These results suggest that the endogenously hyperscreted IL-10 is primarily responsible for the observed decrease in IL-12 released by the frozen cells. They further suggest that the increased amounts of IL-12 secreted by the irradiated PBMCs could account for the previously reported increase in IL-2 and interferon (IFN)-gamma release by the irradiated PBMCs and the radiation-induced immunopotentiation and tumor regression. Considering the pivotal role played by IL-12 in the immune system, and in antimicrobial and antitumor activities, production of only 10% of the normal levels by the frozen cells could have profound impact on patients receiving such frozen PBMCs as stem cell support following myeloablative therapy. Administration of exogenous IL-12 at the time of frozen PBMC transplantations might have a therapeutic value in these patients.
Department of Medicine, Mount Sinai Hospital Medical Center, Chicago, Illinois 60608, USA.
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Venkataraman
D002478:Cells, Cultured; D015925:Cryopreservation; D006801:Humans; D007111:Immunity, Cellular; D016753:Interleukin-10 / Q000096:biosynthesis*; D018664:Interleukin-12 / Q000096:biosynthesis*; D007963:Leukocytes, Mononuclear / Q000276:immunology*; D008070:Lipopolysaccharides / Q000494:pharmacology
D008070:Lipopolysaccharides; D016753:Interleukin-10; D018664:Interleukin-12