Differential Effect of Tacrolimus on Dermal and Intestinal Wound Healing

Tacrolimus, used in organ transplantation, inhibits cellu- lar immune function. Little is known about the effect on dermal and colonic healing. Groups of 10 rats underwent dorsal skin incision, and polyvinyl alcohol sponges were implanted subcutaneously. Beginning at the day of wounding, rats were treated intraperitoneal with 1.0 or 2.0 mg tacrolimus/kg/day. Animals were sacrificed 10 d later to determine wound breaking strength and reparative collagen deposition. Expression of transforming growth factor (TGF)-β, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ was studied in wounds. Groups of 8 rats under- went laparotomy and left colonic anastomosis. These rats were treated by subcutaneous injections with 2.0 or 5.0 mg tacrolimus/kg. Animals were sacrifice d5d later to test colonic bursting pressure and reparative collagen deposition. Expression of TGF-β ,T NF-α, IFN-γ , and CD4 and CD 8i nthe anastomosis was investigated. Tacrolimus impaired dermal healing ( p < .05). This was paralleled by decreased expression of TGF-β (stimulates healing) and increased expression of IFN-γ and TNF-α (both inhibit healing) ( p < .05). In contrast, tacrolimus did not inhibit healing of colonic anastomoses. No effect was seen on the expression of TGF-β, TNF-α, IFN-γ , and CD4 and CD8 in colonic anastomoses. We con- cluded that tacrolimus differentially effects tissue healing and expression of cellular mediators in dermal and intestinal wounds.