Interleukin-12 (IL-12) alone or in synergistic combination with IL-2 for in vitro activation of human bone marrow: differential effects at different time points.
IL-12 augments many effector functions associated with T and NK cells including induction of cytotoxic activity and secretion of various cytokines. In addition, synergistic responses with IL-2 in most of the functions attributed to that cytokine make IL-12 an attractive candidate to have a potential role as an immunotherapeutic agent. We have evaluated the effect of rhIL-12 either alone or in combination with IL-2 on the generation of cytotoxic effectors from normal human bone marrow. IL-12 induced cytotoxic effectors against NK sensitive targets within 24 h of stimulation and this activity was maintained in cultures with IL-12 supplementation for up to 2 weeks tested. The decline in NK activity seen in control cultures over a period of 2 weeks was thus not observed in IL-12 stimulated cultures. In addition, a small increase was also observed in cytotoxic activity against NK resistant Daudi cell targets. IL-12, when combined with a low to intermediate dose of IL-2, led to enhancement in IL-2 induced cytotoxicity against both NK sensitive and resistant targets. However an increase in cytotoxicity against NK resistant targets was evident only after 1 week of stimulation. Cellular yield and number of hematopoietic precursors (LTC-IC, CFU-GM, BFU-e) in IL-12 stimulated cultures was comparable to or higher than control cultures at all the three time points (days 1, 7, 14) tested. In contrast, cultures stimulated with a combination of IL-12/IL-2 showed an increased number of hematopoietic precursors at day 1 followed by a marked decrease in the number of these precursors at day 7 and day 14.(ABSTRACT TRUNCATED AT 250 WORDS)
Verma
U N
UN
Bone Marrow Transplantation Program, Georgetown University Medical Center, Washington DC 20007, USA.
Mazumder
A
A
D001853:Bone Marrow / Q000276:immunology*; D002470:Cell Survival; D002478:Cells, Cultured; D002999:Clone Cells / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004357:Drug Synergism; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000276:immunology; D013997:Time Factors
D007376:Interleukin-2; D018664:Interleukin-12