Induction of Dermal Subcutaneous Inflammation by Recombinant Cachectin/Tumor Necrosis Factor (TNFα) in the Mouse

The ability of cachectin/tumor necrosis factor (TNFα) to induce acute dermal and subcutaneous inflammation was examined in a murine model. A number of other proteins, and diluent alone were examined as controls. After subcutaneous injection into the mouse footpad, recombinant human TNFα(rHuTNFα) induced acute inflammation with an initial marked dermal and subcutaneous neutrophil infiltrate by approximately 3 h, with a peak between 4 and 24 h and resolution by 79 h. Recombinant interleukin-2, cytochrome c, and heat-inactivated rHuTNFα induced negligible inflammation. Recombinant human lymphotoxin (TNFβ), another control protein, also induced acute inflammation in our system. Because and TNFα and TNFβ are partially homologous, they may be acting through a similar mechanism. This pro-inflammatory effect of TNFα may result from chemotactic activity as well as by induction of secondary mediators. Inflammation induced by TNFα was partially suppressed by indomethacin treatment, suggesting that products of the cyclo-oxyganase pathway may mediate a portion of the inflammation involved. Five daily injections of rHuTNFα into the mouse footpad resulted in a predominantly mononuclear infiltrate and focal fibrosis. These results suggest that TNFα may be an important mediator of acute inflammation in vivo and might provide a signal for the production of collagen.