Pathophysiologic alterations induced by tumor necrosis factor.

Work from several laboratories has documented that TNF is toxic in vivo. The data are sufficiently compelling that there is little doubt that this small peptide mediator can induce altered pathophysiology and tissue damage if injected in large quantities. Whereas injection of high-dose, exogenous rHu-TNF results in toxicity, and the production of very high levels in lethal septic shock is detrimental, the exact role of this molecule in inflammation is yet to be defined completely. At low, physiologic levels, TNF may be a necessary component required to orchestrate an effective immune response to a successful resolution. Several works have shown that inhibition of TNF with specific antibodies in models of bacterial infection can decrease survival (Havell, 1987; Echtenacher et al., 1990). Clearly, further work must be done to resolve the issue of the exact role of TNF in organ injury during septic shock.