ISSN:
1534-4681
Keywords:
Interferon gamma
;
Tumor necrosis factor
;
Mouse
;
Sarcoma
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Background: The anticancer role of tumor necrosis factor-alpha (TNF-α) has been limited by toxicity. These experiments evaluate blocking endogenous interferon-gamma (IFN-γ) activity to abrogate TNF-α toxicity. Methods: C57Bl/6 mice bearing MCA 105 tumor were treated with TNF-α and anti-IFN-γ antibody (Ab) to evaluate the effect on the acute lethality of TNF-α and their efficacy as evaluated by tumor growth rate, tumor histology, and survival. Results: Anti-IFN-γ Ab decreased TNF-α lethality. Anti-IFN-γ Ab alone increased tumor growth significantly more than did nonimmune IgG (p2〈0.0001). Tumor-bearing mice that received nonimmune IgG and TNF-α had slower tumor growth (p2〈0.02) and a trend toward improved survival (p=0.07) compared with saline-treated controls. Anti-IFN-γ Ab abrogated the antitumor effect of TNF-α, prevented acute tumor necrosis histologically, and resulted in tumor growth rate and host survival similar to that of controls. The findings in mice that received anti-IFN-γ Ab and high-dose TNF-α were comparable with those in mice that received a lower, equitoxic dose of TNF-α alone. Conclusions: Blocking endogenous IFN-γ accelerates tumor growth in this model and partially abrogates the toxic and antitumor activity of exogenous TNF-α equally. This suggests that blocking endogenous IFN-γ activity is not a useful strategy for limiting TNF-α treatment toxicity.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF02305801
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