Effect of recombinant human tumor necrosis factor on tumor and spleen in mice

The ability of recombinant human tumor necrosis factor (rH-TNF-alpha) to induce regression of sarcoma 180 in vivo was evaluated. The tumor was cured by TNF in the course of 4 weeks. TNF inhibited proliferation of sarcoma 180 cells in vitro, which suggests a direct effect of TNF on tumor cells in vivo. In parallel to the TNF effect on tumor growth, some cell parameters in spleen were investigated. Activation of splenic macrophages was enhanced in vitro. This result suggests that macrophages may participate in the host defense against the tumor. In the first phase of therapy, TNF did not affect the proliferation of splenocytes but increased the transition of G0 into G1 cells. Furthermore, TNF normalized the tumor-induced increase of null cells in tumor-bearing mice. All parameters investigated in spleen reached normal values at the time of tumor regression. Our results suggest that various mechanisms may be involved in TNF-induced regression of sarcoma 180.