ANTITUMOR EFFECT OF INTERLEUKIN-7 IN COMBINATION WITH LOCAL HYPERTHERMIA IN MICE BEARING B16A MELANOMA-CELLS

Interleukin (IL)-7 has been evaluated for its influence, alone or in c ombination with local hyperthermia (LH), on B16a melanoma-bearing mice . Six- to eight-week-old C57BL/6J male mice were inoculated s.c. with 5 x 10(5) tumor cells into the left hind limb. Mice were randomly divi ded into four groups, and treated s.c. with IL-7 (5 ng) or saline as c ontrol, twice a day for three weeks beginning eight days after tumor i noculation. LH, using hot water circulator at 43 +/- 0.2-degrees-C for 30 min, was induced to the limb with tumor twice a week for two weeks . Size of the primary tumor was measured every other day for five week s. Mice were sacrificed five weeks after tumor inoculation. The size o f the primary tumor and the number of lung metastases were reduced in mice treated either with IL-7 or LH alone. As a control for IL-7, gran ulocyte colony stimulating factor (G-CSF) alone had no effect on prima ry tumor size or number of lung metastases. The greatest antitumor eff ect was observed in mice treated with IL-7 in combination with LH. Sur vival was prolonged significantly only in mice treated with IL-7 plus LH compared with that of mice treated with saline. Decreased natural k iller (NK) cell activity, number of Thy1.2 cells, and ratio of L3T4+/L yt2+ cells were associated with tumor growth. These parameters were re stored in mice treated with IL-7 plus LH. Increases in levels of IL-1a lpha, IL-6, tumor necrosis factor (TNFalpha) and interferon (IFNgamma) were associated with an increase in the survival of tumor-bearing mic e treated with IL-7 and/or LH. These results suggest that changes in T -cell, NK cell and cytokines such as IL-1alpha, IL-6, TNF-alpha and IF N-gamma in response to IL-7 and/or LH might account for prolonged surv ival of B16a melanoma-bearing mice and that IL-7 might be useful as a potential antitumor agent combined with other therapy in certain malig nant solid tumors with metastases.