Protective effect of tumor necrosis factor (TNF) obtained by genetic recombination against experimental bacterial or fungal infection

: Recombinant human tumor necrosis factor (rHuTNF) enhanced nonspecific resistance of mice to various bacterial and fungal infections, indicating that the protective effect previously reported by us with serum TNF (sTNF) prepared in mice, could be attributed to this macrophage-derived factor. Comparative assays with both TNF preparations have shown that the protection against the infections challenges was largely correlated with antitumor activity. The protective effect of the rHuTNF preparation, expressed from a cDNA clone in Escherichia coli, was not due to contaminating endotoxin products. Since recombinant TNF and sTNF have no direct bactericidal or anti-fungal activity, the enhanced resistance to infections can be explained by the action of TNF on macrophages and polymorphonuclear cells. The experimental data support the interpretation that TNF has an important role in nonspecific immunity.