Effects of hemorrhagic serum on interleukin-2 generation and utilization

Exposure of normal peripheral blood mononuclear cells (PBMCs) to serum obtained from hemorrhaged animals produces marked depression of mitogen-induced cellular proliferation. In order to examine the mechanism which underlies its suppressive action, the effects of hemorrhagic serum on the production and utilization of interleukin-2 (IL-2) by PBMCs in mitogen-stimulated cultures were investigated. The production of IL-2 by PBMCs obtained from normal animals was reduced by approximately 90% after these cells were washed with hemorrhagic serum for 60 sec at 0 degrees C. Cells cultured in hemorrhagic serum showed greater than 30% reduction in proliferative response to phytohemagglutinin, and no significant change in the degree of suppression was produced by adding recombinant IL-2 to the cell cultures. PBMCs cultured with recombinant IL-2 and hemorrhagic serum, but not mitogen, proliferated significantly less than did cells cultured with IL-2 and normal serum. These findings suggest that although hemorrhagic serum produces a marked decrease in IL-2 generation, the suppressive effects of hemorrhagic serum on mitogen-induced lymphocyte proliferation are not due to this decrease in IL-2 production.