Abstract |
Recombinant interferon-gamma (rIFN-gamma) is currently undergoing clinical trials in cancer patients. In this paper, we assessed the in vivo antitumor effects of this lymphokine in rodents. Recombinant murine IFN-gamma or control medium was injected intraperitoneally for 5 days into mice with subcutaneous Meth A tumors. An injection of a suboptimal dose of endotoxin (2 micrograms) on the fifth treatment day caused significant necrosis of tumors in the IFN-gamma-treated group while causing essentially no necrosis of tumors in the control group. Next, we examined macrophages isolated from rats treated for 9 days with either IFN-gamma or saline. Endotoxin stimulated release of significantly higher amounts of TNF-alpha from macrophages from the IFN-gamma-treated group compared to macrophages from the control group. A polyclonal antiserum against recombinant murine TNF-alpha abrogated all of the TNF cytotoxic activity from these rat macrophage supernatants, while control rabbit serum had no effect. These results provide strong evidence that rIFN-gamma can prime macrophages in vivo for TNF-alpha synthesis.
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Authors | R M Lorence, C K Edwards 3rd, R J Walter, K W Kelley, J A Greager |
Journal | Cancer letters
(Cancer Lett)
Vol. 53
Issue 2-3
Pg. 223-9
(Sep 1990)
ISSN: 0304-3835 [Print] Ireland |
PMID | 2119881
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
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Chemical References |
- Endotoxins
- Recombinant Proteins
- Tumor Necrosis Factor-alpha
- Interferon-gamma
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Topics |
- Animals
- Drug Synergism
- Endotoxins
(administration & dosage)
- Female
- Fibrosarcoma
- Interferon-gamma
(administration & dosage, pharmacology)
- Macrophages
(metabolism)
- Mice
- Mice, Inbred BALB C
- Necrosis
- Rats
- Rats, Inbred Strains
- Recombinant Proteins
- Sarcoma, Experimental
(pathology, therapy)
- Tumor Necrosis Factor-alpha
(biosynthesis)
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