Induction of dermal and subcutaneous inflammation by recombinant cachectin/tumor necrosis factor (TNF alpha) in the mouse.
The ability of cachectin/tumor necrosis factor (TNF alpha) 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 TNF alpha (rHuTNF alpha) 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 rHuTNF alpha induced negligible inflammation. Recombinant human lymphotoxin (TNF beta), another control protein, also induced acute inflammation in our system. Because TNF alpha and TFN beta are partially homologous, they may be acting through a similar mechanism. This pro-inflammatory effect of TNF alpha may result from chemotactic activity as well as by induction of secondary mediators. Inflammation induced by TNF alpha 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 rHuTNF alpha into the mouse footpad resulted in a predominantly mononuclear infiltrate and focal fibrosis. These results suggest that TNF alpha may be an important mediator of acute inflammation in vivo and might provide a signal for the production of collagen.
Sharpe
R J
RJ
Department of Dermatology, Massachusetts General Hospital, Boston 02114.
Margolis
R J
RJ
Askari
M
M
Amento
E P
EP
Granstein
R D
RD
D000208:Acute Disease; D000818:Animals; D003872:Dermatitis / Q000139:chemically induced* / Q000188:drug therapy / Q000473:pathology; D004334:Drug Administration Schedule; D005260:Female; D007213:Indomethacin / Q000627:therapeutic use; D007279:Injections, Subcutaneous; D051379:Mice; D008805:Mice, Inbred A; D008807:Mice, Inbred BALB C; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000633:toxicity*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000633:toxicity*
D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D007213:Indomethacin