Combination Therapy of Tacrolimus and Infliximab Reduces Inflammatory Response and Dysmotility in Experimental Small Bowel Transplantation in Rats

Abstract

Dysmotility of transplanted small bowel results from reperfusion injury and acute rejection. Additional perioperative treatment with infliximab reduces early unspecific inflammatory responses and complements immunosuppressive therapy with tacrolimus.

Difficulties, guidelines and review of developing an acute rejection model after rat intestinal transplantation

“…We used the same score (0-3) to determine rejection [24]. First, Pech et al studied the effects of the immunosuppressive agents when AR appeared; they then studied the specific combination of TAC and infliximab to reduce the inflammatory response and dysmotility; finally, they studied the regeneration, residual function and immunological status after treating rejection [8,9,13]. We initially attempted to reproduce the Pech model in our experiments.…”

“…Furthermore, mortality during the early postoperative days is high, particularly in the orthotopic model if there is no close monitoring similar to that performed on humans [3]. These complications appear to diminish in the heterotopic model [3][4][5][6], although this will never provide the same information as an orthotopic model, which is similar to that experienced in human clinical practice [3,[7][8][9]]. …”

“…We initially used Wistar rats as recipients based on previous publications from our center (not directly related to rejection) [17,[19][20][21]. Because we did not find signs of rejection at the 6th day, we changed to Lewis rats, based on the previously described models [8,9,13,73,74], and given the fully allogenic BN-to-Lewis combination appears to be histoincompatible and rejection has been described as the dominant immunologic response either without or with immunosuppression [56,75]. BN rats have been reported to have "universal donor" qualities for unknown reasons.…”

“…For these reasons, it is difficult to compare the various publications and to establish conclusions before starting as a novice in the field [4][5][6][8][9][10][11][12][13][14][15][16][17][18].…”

Innovations in Immunosuppression for Intestinal Transplantation

“…Increased expression of TNF alpha has been described in episodes of small bowel transplant rejection ( 29 ). Pech et al have described use of anti-TNF therapy to overcome episodes of acute rejection in a rat model of bowel transplant ( 30 ) and also reduce inflammatory infiltrate and dysmotility in the same rat model ( 31 ). Case reports and cohort studies describe beneficial use of anti-TNF to treat patients with acute rejection resistant to conventional therapy, and one report describing use for mucosal inflammation in an intestinal graft ( 32 – 35 ).…”