IFN-γ and TNF-α production in γ-irradiated blood units by mononuclear cells and GVHD prevention

Abstract 

Gamma-radiation of blood products is considered the mainstay of transfusion-associated graft-versus-host disease prevention. Previous studies have detected lymphocyte inhibition rate in blood components just one time after irradiation but there is evidence of cellular variability with production of cytokines at different storage time which could be related with irradiation activity and cellular damage repair. IFN-γ, a Th1 cytokine, and TNF-α, a pro-inflammatory one, had a central role in the stimulation of cellular and inflammatory reactions. In this study whole blood was collected from five volunteer healthy donors and each donor bag was divided into two satellite bags: one of them was exposed to 137Cs-irradiation with a 2500 cGy dose. Samples for cytokine production, detected by ELISA methods, and proliferative response, evaluated by incorporation of H³ thymidine, were taken at the following storage time: 0, 24, 48, 72 and 96 h. The time-response curve of irradiated mononuclear cells from blood bags (BBMC) in mitogenic activation showed a time-related inhibition of cell proliferation with an enhanced response only after 24 h of storage and about 84% inhibition at 96 h. A similar pattern is follow by IFN-γ production after OKT3 stimulation. TNF-α levels both in lipopolysaccharide stimulated or unstimulated cells were always high. This data suggest that BBMC cells maintain the ability to produce cytokines after γ-radiation. On the ground of this study seems to be necessary to evaluate hypothetical risk associated with the administration of cytokine via irradiated blood components.

Keywords:  IFN-γ, TNF-α, γ-irradiation, Blood units, GVHD