TY - JOUR
T1 - Endogenous D‐factor activity partially mediates the toxic but not the therapeutic effects of tumor necrosis factor
AU - Block, Mark I.
AU - Fraker, Douglas L.
AU - Strassmann, Gideon
AU - Billingsley, Kevin G.
AU - Arnold, W. Scott
AU - Perlis, Cliff
AU - Alexander, H. Richard
PY - 1995/10/9
Y1 - 1995/10/9
N2 - 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.
AB - 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.
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U2 - 10.1002/ijc.2910630217
DO - 10.1002/ijc.2910630217
M3 - Article
C2 - 7591212
AN - SCOPUS:0028793326
SN - 0020-7136
VL - 63
SP - 245
EP - 249
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 2
ER -