In vivo effects of recombinant interferon-gamma: augmentation of endotoxin-induced necrosis of tumors and priming of macrophages for tumor necrosis factor-alpha production.
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.
Lorence
R M
RM
Department of Surgery, Cook County Hospital, Chicago 60612.
Edwards
C K
CK
Walter
R J
RJ
Kelley
K W
KW
Greager
J A
JA
D000818:Animals; D004357:Drug Synergism; D004731:Endotoxins / Q000008:administration & dosage*; D005260:Female; D005354:Fibrosarcoma; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D009336:Necrosis; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D012513:Sarcoma, Experimental / Q000473:pathology / Q000628:therapy*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis*
D004731:Endotoxins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma