Effect of systemic administration of mouse recombinant interferon-gamma on the lung tumor metastases in mice.
The purpose of this study was to examine the effective anti-metastatic activity by multiple i.v. administrations of mouse recombinant interferon-gamma (IFN-gamma) against pulmonary metastases of 3LL or B16-BL6 melanoma cells after surgical excision of primary tumors. Multiple treatments with IFN-gamma reduced effectively the incidence of pulmonary tumor metastases. Repeated 4 consecutive treatment modalities with IFN-gamma showed remarkable reduction of lung tumor colonies, and also rendered alveolar macrophages (AM) cytotoxic against B16-BL6 cells. In contrast, 14 consecutive administrations of IFN-gamma at any doses (10(2) and 10(3) U/mouse) could not activate macrophages to become cytotoxic, but were effective in regressing metastases. Thus, antimetastatic activity of IFN-gamma may be due to the stimulation of host immune defense systems such as induction of tumoricidal macrophages, presumably the direct antiproliferative action to tumor cells, or both actions under the appropriate administration conditions. We found that the systemic administration of IFN-gamma under appropriate multiple treatment modalities results in the reduction of the lung metastases and can activate AM to become tumor cytotoxic at relatively low doses (10(2) U). High-dose IFN-gamma in the multiple administration schedule was also effective for the reduction of lung tumor colonies, but strongly suppressed the nonspecific immune function and could not activate tumoricidal properties of AM.
Saiki
I
I
Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Murata
J
J
Saito
S
S
Higashi
N
N
Azuma
I
I
D000818:Animals; D001854:Bone Marrow Cells; D003602:Cytotoxicity, Immunologic; D004306:Dose-Response Relationship, Immunologic; D007275:Injections, Intravenous; D007371:Interferon-gamma / Q000008:administration & dosage* / Q000627:therapeutic use; D008175:Lung Neoplasms / Q000556:secondary / Q000628:therapy*; D008262:Macrophage Activation; D008545:Melanoma / Q000628:therapy*; D051379:Mice; D011994:Recombinant Proteins; D013154:Spleen / Q000166:cytology
D011994:Recombinant Proteins; D007371:Interferon-gamma