Subcutaneous perfusion of tumor necrosis factor induces local proliferation of fibroblasts, capillaries, and epidermal cells, or massive tissue necrosis.

Mouse recombinant tumor necrosis factor (TNF) (or its solvent alone as a control) was administered subcutaneously to mice by a cannula connected to an osmotic minipump. Perfusion at a rate of 35 ng/hr for seven days induced the formation of a tissue mass composed mainly of fibroblasts, collagen, and capillaries. Necrosis (apoptosis) of isolated fibroblasts was observed. Polymorphonuclear leukocytes were abundant after three to four days of perfusion but were absent later. The covering epidermis showed a hyperplastic reaction associated with necrosis of isolated keratinocytes. Perfusion at a rate of 170 ng/hr led, after four to five days, to a massive necrosis. Necrosis was completely prevented by rabbit anti-TNF IgG but not by anti-LPS IgG, irradiation, or administration of indomethacin.