Endogenous D‐factor activity partially mediates the toxic but not the therapeutic effects of tumor necrosis factor

Mark I. Block, Douglas L. Fraker, Gideon Strassmann, Kevin G. Billingsley, W. Scott Arnold, Cliff Perlis, H. Richard Alexander

    Research output: Contribution to journalArticle

    3 Scopus citations

    Abstract

    We have earlier shown that passive immunization against differentiation‐inducing factor/leukemia‐inhibitory factor (D factor) activity improves the survival of endotoxemic mice, suggesting that D factor may contribute to the systemic toxicity associated with tumor necrosis factor (TNF). In the current experiments, TNF induced D‐factor gene expression in various tissues of non‐tumor‐bearing female C57B1/6 mice. Passive immunization against D‐factor significantly improved survival after a lethal TNF challenge in both non‐tumor‐bearing (p2 < 0.02) and tumor‐bearing mice (p2 < 0.01). In mice bearing 10‐days.c. MCA 105 sarcomas, D‐factor antibody alone had no effect on tumor growth as compared with control IgG. Tumor regression and regrowth in mice treated i.v. with TNF was not affected by pre‐treatment with D‐factor antibody, as compared with pre‐treatment with IgG. However, TNF‐treatment‐related mortality was abrogated by pre‐treatment with D‐factor antibody (0% vs. 36% for IgG‐pre‐treated controls). These results indicate that endogenous D‐factor activity contributes to the toxicity but not to the anti‐tumor effects of TNF therapy. With renewed interest in the use of TNF for the treatment of patients with cancer, improved understanding of the role of D factor in mediating the effects of TNF may have important clinical benefits.

    Original languageEnglish (US)
    Pages (from-to)245-249
    Number of pages5
    JournalInternational Journal of Cancer
    Volume63
    Issue number2
    DOIs
    StatePublished - Oct 9 1995

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

    Fingerprint Dive into the research topics of 'Endogenous D‐factor activity partially mediates the toxic but not the therapeutic effects of tumor necrosis factor'. Together they form a unique fingerprint.

  • Cite this

    Block, M. I., Fraker, D. L., Strassmann, G., Billingsley, K. G., Arnold, W. S., Perlis, C., & Alexander, H. R. (1995). Endogenous D‐factor activity partially mediates the toxic but not the therapeutic effects of tumor necrosis factor. International Journal of Cancer, 63(2), 245-249. https://doi.org/10.1002/ijc.2910630217