title: Anti-neoplastic effects of interleukin-4.
abstract: 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 (10(6) cells: right flank; sc) or saline, and sacrificed 10 days postinoculation for assessment of peritoneal macrophage (PMO) 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 less than 0.01), and decreased TNF release but did not alter PM phi TNF-independent anti-tumor responses (P815). In vivo administration of IL-4 significantly decreased tumor growth (P less than 0.05) after 10 days of treatment and significantly prolonged median host survival (P less than 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.
authors.affiliation: Department of Surgery, University of Pennsylvania School of Medicine, Philadelphia 19104.
authors.forename: H P
authors.initials: HP
authors.lastname: Redmond
authors.forename: L
authors.initials: L
authors.lastname: Schuchter
authors.forename: D
authors.initials: D
authors.lastname: Bartlett
authors.forename: C J
authors.initials: CJ
authors.lastname: Kelly
authors.forename: J
authors.initials: J
authors.lastname: Shou
authors.forename: P
authors.initials: P
authors.lastname: Leon
authors.forename: J M
authors.initials: JM
authors.lastname: Daly
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002277:Carcinoma / Q000276:immunology / Q000401:mortality / Q000473:pathology; D005260:Female; D007111:Immunity, Cellular; D015847:Interleukin-4 / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000276:immunology / Q000401:mortality / Q000473:pathology; D008264:Macrophages / Q000378:metabolism / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D013481:Superoxides / Q000378:metabolism; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000502:physiology; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D015847:Interleukin-4