Am. J. Respir. Cell Mol. Biol., Vol 10, No. 2, Feb 1994, 202-206.
Antitumoral potential of aerosolized interferon-gamma in mice bearing lung metastases
R Kessler, S Dumont, J Bartholeyns, E Weitzenblum and P Poindron
Service de Pneumologie, Hopitaux Universitaires, Strasbourg, France.
Cytokines and immune cells are likely to be involved in the control of lung
metastasis. We have therefore investigated the possibility of inhibiting
lung metastases by the means of interferon-gamma (IFN-gamma)
aerosolizations in a murine model of lung cancer. A Lewis lung carcinoma
(3LL) was inoculated in the thigh of C57BL/6 mice. Randomized groups of 10
mice each were then treated by repeated aerosols of IFN- 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 days and
aerosols were continued, in the absence of local recurrence, mice treated
by IFN-gamma aerosols survived longer than did controls (P < 0.05). In
vitro, IFN-gamma exerted no direct antitumoral effect on 3LL cells in
culture. Macrophages recovered from mice receiving IFN-gamma aerosols
showed a higher antiproliferative effect on 3LL cells in vitro than did
controls. Nevertheless, the higher antiproliferative effect of activated
macrophages seems insufficient to explain the difference of survival that
we observed between IFN-gamma- treated mice and controls.
