Differential effect of tacrolimus on dermal and intestinal wound healing.
Tacrolimus, used in organ transplantation, inhibits cellular 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)-beta, tumor necrosis factor (TNF)-alpha, and interferon (IFN)-gamma was studied in wounds. Groups of 8 rats underwent laparotomy and left colonic anastomosis. These rats were treated by subcutaneous injections with 2.0 or 5.0 mg tacrolimus/kg. Animals were sacrificed 5 d later to test colonic bursting pressure and reparative collagen deposition. Expression of TGF-beta, TNF-alpha, IFN-gamma, and CD4 and CD8 in the anastomosis was investigated. Tacrolimus impaired dermal healing (p < .05). This was paralleled by decreased expression of TGF-beta (stimulates healing) and increased expression of IFN-gamma and TNF-alpha (both inhibit healing) (p < .05). In contrast, tacrolimus did not inhibit healing of colonic anastomoses. No effect was seen on the expression of TGF-beta, TNF-alpha, IFN-gamma, and CD4 and CD8 in colonic anastomoses. We concluded that tacrolimus differentially effects tissue healing and expression of cellular mediators in dermal and intestinal wounds.
Schäffer
Michael
M
Department of Surgery, Chirurgische Universitätsklinik, Bochum-Langendreer, Germany. micheal.schaeffer@kk-bochum.de
Fuchs
Nico
N
Völker
Julia
J
Schulz
Tim
T
Kapischke
Matthias
M
Viebahn
Richard
R
D000818:Animals; D020405:Dermis / Q000276:immunology* / Q000378:metabolism / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007371:Interferon-gamma / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000276:immunology* / Q000601:surgery; D011183:Postoperative Complications; D051381:Rats; D017207:Rats, Sprague-Dawley; D013530:Surgical Wound Infection; D016559:Tacrolimus / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000276:immunology
D007166:Immunosuppressive Agents; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D016559:Tacrolimus