Antitumor Effect of Interleukin‐1β in the Double Grafted Tumor System

Abstract

The antimetastatic effect of recombinant human interleukin‐1β (rIL‐1β) in a new experimental mouse model was studied. Intratumoral administration of IL‐1β strongly inhibited the growth of Meth‐A solid tumors in male BALB/c mice and led to a complete regression of tumors and resistance to reinoculated tumor. Subsequently, the anti‐metastatic effect of IL‐1β was examined in the double grafted tumor system, in which mice first received simultaneous intradermal inoculations of Meth‐A in both right (106 cells) and left (2×105 cells) flanks and were then injected with 0.2 μg of IL‐1β in the right tumor on days 3, 4 and 5. IL‐1β significantly inhibited the growth of the left, non‐treated tumor. When mice received only an inoculation of Meth‐A (2×105 cells) in the left flank and were injected subcutaneously with IL‐1β into the right flank on day 3 (single tumor system), there was no inhibition of the growth of the left, non‐treated tumor. These findings suggest that intratumoral IL‐1β immunotherapy in one region has an effect on tumor growth in another region. Immunized spleen cells were taken from mice which had been cured by the intratumoral administration of IL‐1β. Adoptive transfer of the immunized spleen cells caused the complete regression of Meth‐A tumors. These results suggest that intratumoral administration of IL‐1β might induce cytotoxic cells in the left non‐treated tumor of the double grafted tumor system and bring about the regression of metastatic tumors. On the other hand, recombinant tumor necrosis factor was effective only on the treated, right tumor, having no effect on the distant, left tumor in the double grafted tumor system. Recombinant interleukin‐2 was effective on neither the right tumor nor the left tumor in this system. These results show that there are major differences of antitumor mechanism among cytokines.