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

Abstract

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, thein 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 hypersecreted 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)-γ 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.