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

M. I. Block, D. L. Fraker, G. Strassmann, Kevin Billingsley, W. S. Arnold, C. Perlis, H. R. Alexander

Research output: Contribution to journalArticle

3 Citations (Scopus)

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-day s.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 - 1995
Externally publishedYes

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Poisons
Therapeutic Uses
Tumor Necrosis Factor-alpha
Passive Immunization
Immunoglobulin G
Neoplasms
Antibodies
Therapeutics
Leukemia Inhibitory Factor
Survival
Sarcoma
Gene Expression
Mortality
Growth

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Endogenous D-factor activity partially mediates the toxic but not the therapeutic effects of tumor necrosis factor. / Block, M. I.; Fraker, D. L.; Strassmann, G.; Billingsley, Kevin; Arnold, W. S.; Perlis, C.; Alexander, H. R.

In: International Journal of Cancer, Vol. 63, No. 2, 1995, p. 245-249.

Research output: Contribution to journalArticle

Block, M. I. ; Fraker, D. L. ; Strassmann, G. ; Billingsley, Kevin ; Arnold, W. S. ; Perlis, C. ; Alexander, H. R. / Endogenous D-factor activity partially mediates the toxic but not the therapeutic effects of tumor necrosis factor. In: International Journal of Cancer. 1995 ; Vol. 63, No. 2. pp. 245-249.
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