ACQUIRED-IMMUNITY TO TNF - EFFECTS ON INTESTINAL WOUND-HEALING

Increased concentrations of tumor necrosis factor (TNF) damage normal tissue and produce a shock-like syndrome-changes that can be prevented with antibody-specific antisera. These findings suggest that TNF-stim ulated immunity should protect normal tissue and promote wound healing , To test this hypothesis, 30 Fischer 344 rats (150-200 g) were serial ly immunized against TNF (20 mu g/kg). Convalescent sera assayed (micr o-ELISA) for circulating antibodies revealed titers (2.54 +/- 0.08 au) significantly higher (P < 0.00001) in immunized animals than in nonim munized controls (0.11 +/- 0.06 au). Following this, 10 immunized (Gro up I), 10 nonimmunized (Group II), and 10 control rats underwent parti al cecectomy with primary anastomosis. Animals from Groups I and II re ceived TNF (25 mu g/kg) while controls received saline intravenously o n Postoperative Days 1, 3, and 5. Animals were then sacrificed to dete rmine: (1) hydroxyproline content of the anastomosis, (2) mitochondria l respiratory control ratio, and (3) pyruvate dehydrogenase activity o f the muscle. We found that (1) exposure to increased concentrations o f TNF (Group II) depresses (P < 0.01) biologic markers of wound healin g and (2) acquired immunity to TNF (Group I) eliminates this response. In conclusion, acquired immunity to TNF protects the healing intestin al anastomosis from the effects of exposure to increased levels of TNF . (C) 1996 Academic Press, Inc.