Synergistic and overlapping activities of tumor necrosis factor-alpha and IL-1.
TNF-alpha and IL-1 induce the production of PGE2 from human chondrosarcoma, fibrosarcoma, and carcinoma cell lines. When combined at sub-optimal concentrations, TNF-alpha and IL-1 synergistically stimulate PGE2 production. The synergy of TNF-alpha and IL-1 on the induction of PGE2 is partially neutralized by specific antibodies. In vitro, human rTNF-alpha is directly cytotoxic to several human transplantable tumor cell lines. These include a human carcinoma, human chondrosarcoma, and a human transformed fibroblast cell line. The cytotoxic effect of TNF-alpha was abrogated by a specific, neutralizing, polyclonal antibody. IL-1 had no direct cytotoxic effect on these cell lines; however, IL-1 enhanced the cytotoxic effects of TNF-alpha. The synergy of these two cytokines in the cytotoxic assay was neutralized by the addition of specific neutralizing antibodies.
Last-Barney
K
K
Department of Immunology, Boehringer Ingelheim Pharamaceuticals, Inc., Ridgefield, CT 06877.
Homon
C A
CA
Faanes
R B
RB
Merluzzi
V J
VJ
D002460:Cell Line; D002813:Chondrosarcoma / Q000276:immunology / Q000378:metabolism; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D015232:Dinoprostone; D004357:Drug Synergism; D005354:Fibrosarcoma / Q000276:immunology / Q000378:metabolism; D006801:Humans; D007375:Interleukin-1 / Q000494:pharmacology*; D011458:Prostaglandins E / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007375:Interleukin-1; D011458:Prostaglandins E; D014409:Tumor Necrosis Factor-alpha; D015232:Dinoprostone