Isolated single-lung perfusion with TNF-alpha in a rat sarcoma lung metastases model

We conducted a trial of isolated lung perfusion using tumor necrosis factor (TNF) in an experimental sarcoma lung metastasis model. In an in vitro experiment, methylcholanthrene-induced sarcoma cells were incubated for 48 hours with 42 micrograms/mL of either human or murine TNF. Controls were incubated with Hank's balanced salt solution. In an in vivo experiment, 23 F344 rats were injected with 10(7) methylcholanthrene-induced sarcoma cells. On day 7, 4 animals were perfused with 210 micrograms of murine TNF, 5 animals were perfused with 420 micrograms of murine TNF, 10 animals underwent isolated lung perfusion with 420 micrograms of human TNF, and 4 animals were injected systemically with 420 micrograms of human TNF. Animals were sacrificed on day 14 and the lung nodules counted. The cells incubated with murine TNF exhibited a 21% decrease in growth (p = 0.07); cells incubated with human TNF showed a 37% decrease in growth (p < 0.05). Animals perfused with 210 micrograms/mL of murine TNF and animals treated by systemically administered human TNF showed no tumor response. Animals perfused with 420 micrograms/mL of murine TNF had 7.8 +/- 14.2 nodules on the left lung and 58.5 +/- 66.0 nodules on the right lung (p = 0.07). Animals perfused with 420 micrograms/mL of human TNF had 21.7 +/- 18.3 nodules on the left lung and 91.7 +/- 66.2 nodules on the right lung (p < 0.01). On the basis of these findings, we conclude that isolated lung perfusion with TNF can be done safely in the rat and is effective in decreasing the growth of sarcoma lung metastases.