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KMID : 0360319930250050751
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Journal of Korean Cancer Research Association
1993 Volume.25 No. 5 p.751 ~ p.759
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Effects of Cytokine Combinations on Lymphokine-Activated Killer(LAK) Cell Generation
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성인환
최지영/윤환중/전의건/길준영/조덕연/김삼용/노홍규
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Abstract
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Lymphokine-activated killer cells(LAK) have limited clinical activity against human cancers although they were active in vitro studies. The current study was undertaken to investigate the effects of various cytokines and its combinations on LAK
cell
generation in vitro to evaluate any synergism of cytokines on LAK cell induction.
Purified mononuclear cells(MNC) obtained from peripheral blood of three healthy subjects were cultured for 4 days with various cytokines and then tested for LAK activity as assessed by lysis of Daudi in a 4 hour 51Cr release assay. The data are
presented as per cent specific lysis or lytic units(LU30) per 10E7 effectors when possible.
1) In kinetic studies for LAK cell generation. maximal LAK activity against Daudi cells was generated after 4 days of culture with IL-2. LAK activity generation was IL-2 dose-dependent. IL-1 induced LAK activity lower than that by IL-2. IL-4 was
inactive in inducing LAK activity.
2) Maximal interferon-induced LAK cytotoxicity occurred after 24 hr of culture using 1000U/ml IFN-a and 1000 U/ml IFN-γ. The magnitude of IFN-a-induced LAK activity was similar to that induced by IFN-γ. IFN- induced LAK activity was transient
and
waned by 48 hr of culture.
3) IL-1 synergized with IL-2 in the induction of LAK activity. The most effective doses were 10 U/ml IL-2 with 100 U/ml IL-1. IL-4 inhibited LAK activity when added at the start of culture of lymphocytes with IL-2, but IL-4 slightly enhanced LAK
activity in lymhocytes preactivated by IL-2.
These results suggest that IL-2, IL-1, IFN-a, IFN-γ, and probably IL-4 are important biological agents inducing LAK cell activity and combinations of IL-2 with IFNs, IL-1 or IL-4 could serve to increase LAK cell generation in vivo as was
demonstrated
in vitro.
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KEYWORD
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