Antitumor effect of interleukin-1 beta in the double grafted tumor system

The antimetastatic effect of recombinant human interleukin-1 beta (rIL-1 beta) in a new experimental mouse model was studied. Intratumoral administration of IL-1 beta 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-1 beta was examined in the double grafted tumor system, in which mice first received simultaneous intradermal inoculations of Meth-A in both right (10(6) cells) and left (2 X 10(5) cells) flanks and were then injected with 0.2 micrograms of IL-1 beta in the right tumor on days 3, 4 and 5. IL-1 beta significantly inhibited the growth of the left, non-treated tumor. When mice received only an inoculation of Meth-A (2 X 10(5) cells) in the left flank and were injected subcutaneously with IL-1 beta 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-1 beta 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-1 beta. Adoptive transfer of the immunized spleen cells caused the complete regression of Meth-A tumors. These results suggest that intratumoral administration of IL-1 beta might induce cytotoxic cells in the left non-treated tumor of the double grafted tumor system and bring about the regression of metastatic tumors.(ABSTRACT TRUNCATED AT 250 WORDS)