Interleukin-12 (IL-12) enhances lysis of non-lymphoid 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 minimal residual disease (MRD) in AML patients. The ability to enhance lysis 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 vitro lysis of the non-lymphoid leukemia cell lines in a standard 51Chromium release assay. Effector cells from normal volunteers were incubated with varying concentrations of IL-12 or IL-2 for 18-20 h, then the 51Cr-labeled target cells from five different cell lines of AML origin were added for 4 h. Percent lysis was determined and plotted over four effector:target (E:T) ratios. Our results indicated that IL-12 was able to enhance lysis of all cell lines tested at > or =5 units/ml. When IL-2 was added to the culture at a low dose along with IL-12, there appeared to be a synergistic effect. Although anti-gamma interferon was able to inhibit the cytolytic potential of effectors activated by IL-12, the lysis could not be completely blocked. Thus, it appears that IL-12 has the ability to stimulate NK lysis indirectly through the induction of gamma interferon as well as an alternate mechanism not related to gamma interferon. Thus, IL-12 may have a beneficial role in the treatment of non-lymphoid leukemia.
Pediatric Hematology-Oncology at the University of Arkansas for Medical Sciences, Arkansas Children's Hospital, Little Rock 72202, USA.
K C
KC
Stine
B A
BA
Warren
D L
DL
Becton
D000208:Acute Disease; D016923:Cell Death / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000276:immunology*; D007951:Leukemia, Myeloid / Q000276:immunology* / Q000473:pathology; D014407:Tumor Cells, Cultured
D007376:Interleukin-2; D018664:Interleukin-12; D007371:Interferon-gamma