Recombinant factor XIII improves established experimental colitis in rats

Factor XIII (FXIII) is the plasma-borne transglutaminase involved in fibrin clot stabilization and wound healing. FXIII levels in the plasma of patien ts with inflammatory bowel diseases are lower than normal and there is a si gnificant inverse correlation of FXIII levels with clinical severity. Moreo ver, uncontrolled studies report beneficial effects of FXIII supplementatio n in patients resistant to conventional therapies. We investigated the effe cts of intravenous recombinant FXIII (rFXIII) treatment in experimentally i nduced rat colitis to verify that FXIII was the active agent in plasma FXII I concentrates and to better understand the potential therapeutic use of th is protein. Colitis was induced by instillation of 12% 2,4,6-trinitrobenzen esulfonic acid (TNBS) in 50% ethanol into the colon of male Wistar rats. Ra ts were treated with 0.65 mg/kg rFXIII or vehicle (intravenously) daily for 10 days. Treatment was started either immediately after TNBS/EtOH instilla tion (to evaluate effects on developing lesions) or seven days later (to ev aluate effects on established lesions). In both cases rats were killed eith er immediately after the end of treatment (to evaluate immediate effects) o r 17 days later (to evaluate long-lasting effects). The effects of rFXIII w ere compared to positive (5-amino-2-hydroxybenzoic acid) control over a 35- day time course. The severity of lesions was determined by colon weight and macroscopic and histologic scores. Transglutaminase activity was measured in both colon tissue and serum. rFXIII treatment reduced lesion severity si gnificantly not only in developing but also in established lesions. Improve ments in healing persisted at least 18 days after treatment was discontinue d. Serum and tissue transglutaminase levels were restored by rFXIII treatme nt. In conclusion; pure rFXIII is as effective as plasma FXIII concentrates in a rat model of experimental colitis. In addition, rFXIII significantly improves the healing of preexisting lesions, a characteristic useful in tre atment of human inflammatory bowel diseases.