ANTITUMORAL POTENTIAL OF AEROSOLIZED INTERFERON-GAMMA IN MICE BEARINGLUNG METASTASES

Cytokines and immune cells are likely to be involved in the control of lung metastasis. We have therefore investigated the possibility of in hibiting lung metastases by the means of interferon-gamma (IFN-gamma) aerosolizations in a murine model of lung cancer. A Lewis lung carcino ma (3LL) was inoculated in the thigh of C57BL/6 mice. Randomized group s of 10 mice each were then treated by repeated aerosols of EFN-gamma (4,000 U/mouse) of aerosols of a Hanks' solution as controls. When the animals were killed at 18 days, the number of lung metastatic nodules was significantly reduced (by 50%; P < 0.01) after IFN-gamma aerosols , compared with controls. When the primary tumor was resected at 18 da ys and aerosols were continued, in the absence of local recurrence, mi ce treated by IFN-gamma aerosols survived longer than did controls (P < 0.05). In vitro, IFN-gamma exerted no direct antitumoral effect on 3 LL cells in culture. Macrophages recovered from mice receiving IFN-gam ma aerosols showed a higher antiproliferative effect on 3LL cells in v itro than did controls. Nevertheless, the higher antiproliferative eff ect of activated macrophages seems insufficient to explain the differe nce of survival that we observed between IFN-gamma-treated mice and co ntrols.