[34] Human tumor necrosis factor

This chapter explains the human tumor necrosis factor (TNF). TNF is demonstrated to have cytostatic and cytolytic action on several tumor cell lines, without any effect on normal cells. The agents used to prime for TNF production in mice are shown to cause massive hyperplasia of macrophages in liver and spleen, suggesting that macrophages are the cellular source of TNF. Attempts to produce sufficient TNF either from serum of primed animals or from macrophages derived from human blood have failed due to several reasons. Only trace amounts (nanogram quantities) of TNF protein is produced by macrophages and scale up is difficult due to the limited number of available cells. Several cell lines of lymphocytic and monocytic origin were screened for the production of TNF. The biological activity of TNF in vitro is monitored by the lysis of mouse L-929 cells after exposure to TNF for 48 hr. The sensitivity of this assay can be enhanced almost 10-fold when L-929 cells are pretreated with actinomycin D or mitomycin C. for the production of TNF. Thus, the chapter briefly describes TNF bioassay.