ANTI-INTERLEUKIN-4 ANTIBODY AND INDOMETHACIN SYNERGISTIC EFFECT ON B16 MELANOMA TUMOR PROGRESSION

B16 melanoma-bearing mice were treated with anti-interleukin 4 antibod y, indomethacin or its combination to evaluate the ability of the prim ary tumor to induce lung metastasis and the antitumor host response. F low cytometry of tumor cells incubated with sera from tumor-bearing mi ce showed B16 melanoma to induce a significant antitumor humoral respo nse (39.0 +/- 1.1% positive cells versus 1.8 +/- 0.9% in the control). The treatment of tumor-bearing mice with antimouse anti-interleukin 4 monoclonal antibody plus indomethacin significantly increased (P < .0 1) the mean value of lung metastasis (from 6.1 +/- 3.0 in the controls to 50.8 +/- 21.8). Also, a significant increase in natural cytotoxici ty against tumor cells was observed when both peripheral blood mononuc lear cells and splenocytes were used as effector cells. In contrast, a n antibody-dependent cellular cytotoxicity decrease was found with eff ector cells from both normal and tumor-bearing mice. In the former, th e antibody-dependent cellular cytotoxicity decrease was 49.4% and 58.4 % (P < .05) for peripheral blood mononuclear cells and splenocytes, wh ereas in the second case the decrease was 40.7% (P < .05) and 29.1% (P < .01), respectively. These results suggest that an efficient antibod y-dependent cellular cytotoxicity response might be necessary to secur e an effective host antitumor immune response.