The Journal of Immunology, Vol 141, Issue 2 527-530, Copyright © 1988 by American Association of Immunologists

ARTICLES

Synergistic and overlapping activities of tumor necrosis factor-alpha and IL-1

K Last-Barney, CA Homon, RB Faanes and VJ Merluzzi
Department of Immunology, Boehringer Ingelheim Pharamaceuticals, Inc., Ridgefield, CT 06877.

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.

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