TNF-ALPHA AND IFN-GAMMA REVERSE IL-4 INHIBITION OF LYMPHOKINE-ACTIVATED KILLER-CELL FUNCTION

Recombinant IL-4 inhibits IL-2-induced lymphokine-activated killer (LAK) cell development of PBMC. We evaluated the effect of various cytokines in reversing IL-4-mediated LAK inhibition. PBMC were cultured in IL-2 (10-1000 u/ml) with or without IL-4 (2-100 u/ml) and tested for cytotoxicity against the NK-sensitive K562 cells and NK-resistant UCLA-SO-M14 cells. Addition of IL-4 at the beginning of culture suppresses LAK activity in a dose-dependent fashion. Addition of IFN-γ or TNF-α partially reverses IL-4-mediated inhibition (30-100%) in a dose-dependent fashion. IFN-γ and TNF-α must be added within the first 24 hr of initiating culture in order to reverse IL-4 inhibition. Furthermore, IFN-γ and TNF-α are most effective at reversing IL-4 inhibition at low concentrations of IL-2 (< 100 u/ml). Addition of other IL-2-induced cytokines such as GM-CSF (50 u/ml), M-CSF (250 u/ml), and IFN-α (10-10,000 u/ml) fails to reverse IL-4 inhibition. In addition to suppression of LAK induction, IL-4 also inhibits IL-2-induced IFN-γ and TNF-α protein production in PBMC. The reversal of IL-4-mediated LAK inhibition by TNF-α and IFN-γ may therefore be due to resupply of these endogenously suppressed cytokines. © 1990.