In vivo effects of recombinant interferon-γ : augmentation of endotoxin-induced necrosis of tumors and priming of macrophages for tumor necrosis factor-α production

Abstract Recombinant interferon-γ (rIFN-γ) 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-γ 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 μg) on the fifth treatment day caused significant necrosis of tumors in the IFN-γ-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-γ or saline. Endotoxin stimulated release of significantly higher amounts of TNF-α from macrophages from the IFN-γ-treated group compared to macrophages from the control group. A polyclonal antiserum against recombinant murine TNF-α 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-γ can prime macrophages in vivo for TNF-α synthesis.