ANTINEOPLASTIC EFFECTS OF INTERLEUKIN-4

Interleukin-4 (IL-4) is a cytokine, with potential anti-neoplastic effects. This study examined the effects of IL-4 on host anti-tumor responses in a murine model. C57/B16 mice (n = 40) were randomized to receive Lewis lung carcinoma (106 cells: right flank; sc) or saline, and sacrificied 10 days postinoculation for assessment of peritoneal macrophage (PMØ) anti-tumor mechanisms [superoxide anion generation (O2-), tumor necrosis factor (TNF), and TNF-independent (P815) cytotoxicity], splenocyte mixed lymphocyte response (MLR) (Balb/c stimulator), and cytotoxic lymphocyte generation (CTL against P815). Cells were cultured ± IL-4 (100 U/ml). In a second study, 20 mice received Lewis lung implants (sc) and were randomized on Day 21 to receive daily IL-4 (1000 U/mouse; ip) or saline. Tumor volumes and median survival were assessed. Tumor necrosis factor-independent cytotoxicity (O2-, MLR and CTL) was impaired in the tumor-bearing (TB) study group. Interleukin-4 administered to cultured cells from TB mice enhanced O2-, as well as MLR and CTL (P < 0.01), and decreased TNF release but did not alter PMØ TNF-independent anti-tumor responses (P815). In vivo administration of IL-4 significantly decreased tumor growth (P < 0.05) after 10 days of treatment and significantly prolonged median host survival (P < 0.05). These findings indicate the therapeutic potential of IL-4 in the TB host which may function through downregulation of TNF production while potentiating certain T cell-dependent and independent anti-tumor immune mechanisms. © 1992.