In addition to its antiviral and antibacterial activities, recombinant human γ-interferon (rHuIFN-γ) can exert an antiproliferative effect on human cell lines. The mechanisms involved in this antiproliferative activity are poorly understood, but it is known that IFN-γ can induce indoleamine 2,3-dioxygenase, which enhances tryptophan metabolism and thus depletes the cellular pool of this amino acid. In the present study we have examined the effect of different tryptophan concentrations on the antiproliferative activity of rHuIFN-γ on four human tumor cell lines, HeLa 229, HEp-2, A549, and T24. Cells were grown in the presence of rHuIFN-γ (0.01 to 100 ng/ml) and/or tryptophan (10 to 400 µg/ml) for 7 days at which time they were counted. rHuIFN-γ (4 ng/ml) inhibited the growth of A549 and T24 cells by 50%. Hep-2 and HeLa 229 cells were more sensitive to the rHuIFN-γ induced antiproliferative effects, requiring only 0.4 ng/ml for a 50% inhibition. Addition of tryptophan to the media at concentrations from 10 to 100 µg/ml resulted in a significant blockage of the antiproliferative activity of rHuIFN-γ. For example, when 50 µg/ml of tryptophan were added to the media, 10 times more rHuIFN-γ (4 ng/ml) was needed to inhibit HeLa 229 cells by 50% of the control. The A549 was the most sensitive cell line to the modulatory activity of the tryptophan. Addition of 10 µg/ml of tryptophan changed the amount of rHuIFN-γ needed to produce a 50% inhibition from 4 ng/ml to 100 ng/ml. In summary, in the four human tumor cell lines tested, the antiproliferative activity of rHuIFN-γ could be modulated by the concentration of tryptophan in the media.

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