INTERLEUKIN-12 (IL-12) ENHANCES LYSIS OF NONLYMPHOID LEUKEMIA-CELL LINES IN-VITRO

IL-2 augments the ability of natural killer (NK) cells to kill myeloid leukemia cells in vitro, and may have a role in the eradication of mi nimal residual disease (MRD) in AML patients. The ability to enhance l ysis of AML cells without the toxicity of IL-2 would be a significant improvement in the use of biologics against AML. Recent interest in IL -12 suggested that this cytokine might meet these criteria. The aim of this study was to evaluate the ability of IL-12 to enhance the in vit ro lysis of the non-lymphoid leukemia cell lines in a standard (51)Chr omium release assay. Effector cells from normal Volunteers were incuba ted with varying concentrations of IL-12 or IL-2 for 18-20 h, then the Cr-51-labeled target cells from five different cell lines of AML orig in were added for 4 h. Percent lysis was determined and plotted over f our effector:target (E:T) ratios. Our results indicated that IL-12 was able to enhance lysis of all cell lines tested at greater than or equ al to 5 units/ml. When IL-2 was added to the culture at a low dose alo ng with IL-12, there appeared to be a synergistic effect. Although ant i-gamma interferon was able to inhibit the cytolytic potential of effe cters activated by IL-12, the lysis could not be completely blocked. T hus, it appears that IL-12 has the ability to stimulate NK lysis indir ectly through the induction of gamma interferon as well as an alternat e mechanism not related to gamma interferon. Thus, IL-12 may have a be neficial role in the treatment of non-lymphoid leukemia.