Tumour-necrosis factor from the rabbit. V. Synthesis in vitro by mononuclear phagocytes from various tissues of normal and BCG-injected rabbits

Abstract

Tumour-necrosis factor (TNF) is an anti-tumour factor released into the serum of BCG-primed rabbits after i.v. injection of endotoxin. Although negligible amounts of TNF are produced in normal, unprimed animals after endotoxin injection, monocytes from these rabbits can produce TNF after endotoxin challenge in vitro. This paper (a) establishes the optimal conditions for TNF production in vitro by mononuclear phagocytes from various tissues and (b) compares tissues from normal and BCG-injected rabbits for TNF production in vitro. Optimal amounts of TNF are produced by mononuclear phagocytes in the presence of endotoxin. The TNF is newly synthesized, mainly in the first 7 h of culture, and has similar gel-filtration and ion exchange behaviour irrespective of its source. For both normal and BCG-injected rabbits, alveolar and peritoneal macrophages are the most potent producers, followed by blood monocytes, spleen macrophages and marrow cells. The liver is also an important site of TNF synthesis. In the tissues of BCG-injected rabbits there are more mononuclear phagocytes than in normal rabbits, and these cells have enhanced capacity to produce TNF. Taking both factors into account it can be calculated that, after injection of endotoxin in vivo, over 20 X more TNF would be produced by BCG rabbits than normal rabbits, assuming that the major sources of production are the lungs, blood, spleen and liver.