TUMOR-NECROSIS-FACTOR-ALPHA INHIBITS WOUND-HEALING IN THE RAT

This work was undertaken to study the effects of tumor necrosis factor-alpha (TNF-alpha/cachectin) on developing granulation tissue in rats. Cylindrical hollow sponge implants were used as an inductive matrix for the growth of granulation tissue. In the two test groups the implants were injected daily for 4 days with a solution containing either 50 or 200 ng of TNF-alpha, while the implants of the control group were treated correspondingly with phosphate-buffered saline solution only. Analyses of granulation tissue and wound fluid in the sponge implants were carried out 7, 14 and 21 days after implantation. In histological specimens the ingrowth rate of granulation tissue into sponge was significantly lower after 7 days in the group treated with 200 ng of TNF-alpha. No such an effect was observed after 14 or 21 days. After 7 days, the mean amounts of nucleic acids reflecting cellularity in the granulation tissue decrease dose-dependently, but nonsignificantly, in the groups treated with TNF-alpha. Simultaneously, the accumulation of collagen hydroxyproline of the sponge was significantly lower the group treated with 200 ng of TNF-alpha than in the controls (-30%, one-way analysis of variance). This effect was not observed after 14 or 21 days. No significant differences were detected in the amounts of nitrogen, hemosamines and uronic acids between the groups, reflecting unchanged accumulation of glycosaminoglycans in the developing granulation tissue. No difference was detected in interleukin-1 activity of the wound fluid between the control and TNF-alpha-treated groups. These findings demonstrate that TNF-alpha treatment inhibits wound healing during its inflammatory phase by decreasing production of new granulation tissue. However, this effect disappears at later phases of healing.