UMOR necrosis factor c~(TNF) and tumor necrosis factor~(lymphotoxin) are two cytokines produced primarily by macrophages and lymphocytes, respectively. These cytokines are recognized by the same cell surface receptors and are associated with similar biological activities. Some of the well-known TNF effects include septic shock, cytotoxicity, inflammation, and cachexia. The role of TNF in the pathology of these disease states has been inferred from studies of:(a) the effects of TNF administration in both patients and animal models;(b) the effects of neutralizing anti-TNF antibody,(Fiers, 1991; Vassalli, 1992); and (c) the phenotype of mice made deficient for the 55-kD TNF receptor by gene targeting (Pfeffer et al., 1993; Rothe et al., 1993).

Of these major responses associated with TNF, the septic shock syndrome results from the reaction of the body to parasitic, bacterial or viral infections. Following endo-or exotoxic challenge, TNF is produced by macrophages and is believed to augment their production and their phagocytic/cytotoxic actions. The effects of septic shock can be mimicked by higher doses of TNF and these effects can be prevented by the prior injection of anti-TNF antibody (Vassalli, 1992). Direct cytotoxicity has been a widely cited effect to account for the harmful effects of TNE However, TNF kills most cells only in the presence of metabolic inhibitors like actinomycin D and cycloheximide (CHX), conditions that are nonphysiological. Notwithstanding, the phenomenon of TNF-induced cell killing has attracted great attention and cells that are killed by TNF alone have become popular model systems for TNF cytotoxicity (see Heller et al., 1992). Inflammation as a general consequence of TNF action is likely to be related to TNF stimulation of arachidonic acid (AA) release, activation of cytosolic phospholipase A2 (cPLA2) and production of pro-inflammatory mediators like prostaglandins and leukotrienes. TNF's role in