Four human renal carcinoma cell lines (786-0, CaKi-1, TK-10 and TK-164) were studied in vitro for susceptibility to human recombinant interferon-gamma (IFNγ) and/or human recombinant tumor necrosis factor (TNF). All four cell lines tested demonstrated a dose dependent sensitivity to the cytotoxic effects of TNF alone. The degree of sensitivity varied for each cell line. IFNγ alone also mediated a dose dependent antiproliferative effect in three of the four cell lines. Combinations of IFNγ and TNF produced diverse inhibitory effects. Preincubation of the cells for various time intervals with noninhibitory concentrations of IFNγ prior to the addition of TNF resulted in distinct effects for each cell line. Pretreatment of enhanced the cytotoxic effect of TNF for some cell lines; however, others became less suceptible and some demonstrated enhanced proliferation in the presence of both agents. Optimal pretreatment times also varied from cell line to cell line. These results demonstrate variability in responsiveness by renal carcinoma cell lines to combination IFNγ and TNF treatments and suggest that timing as wll as concentration may be important in in vivo therapy.
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