Short-term anti-CD4 plus anti-TNF-alpha receptor treatment in allogeneic small bowel transplantation results in long-term survival.
BACKGROUND
Despite improved immunosuppression, intestinal transplantation is still complicated by severe rejection episodes. To further improve immunosuppressive concepts, we evaluated an anti-CD4 antibody and an anti-tumor necrosis factor (TNF)-alpha monoclonal antibody for their immunosuppressive efficacy in the standard rat model of intestinal transplantation.


METHODS
Intestinal transplantation was performed in the DA to Lewis combination, and recipients were treated perioperatively with either the anti-CD4 antibody RIB5/2 (day -1, 0, postoperative days 1, 2, 4, 7, 10, 14, 17, and 21), the anti-TNF antibody etanercept (60 min before reperfusion, postoperative days 3, 6, and 9) or a combination of both. Survival, histology and expression of immunologic mediator genes on days 3 and 4 after transplantation were investigated.


RESULTS
Treatment with anti-CD4 antibody alone (19.71+/-5.94) and the antibody combination (171.58+/-122.76) prolonged survival. The chemokine MIP-1alpha was significantly decreased in both anti-CD4 antibody treatment groups, possibly indicating an additional effect of the TNF-alpha blockade on the immune modulation by RIB5/2.


CONCLUSIONS
Our study demonstrated long-term graft survival in short-term treatment with a combination of an anti-CD4 antibody and a TNF-alpha antibody in more than 50% of the recipients of intestinal grafts. Such a combined approach could also be useful in clinical small bowel transplantation.
Langrehr
Jan M
JM
Department of General, Visceral and Transplantation Surgery, Charité Universitätsmedizin Berlin Campus Virchow-Klinikum, Humboldt-Universität zu Berlin, Berlin, Germany. jan.langrehr@chaite.de
Gube
Kathrin
K
Hammer
Markus H
MH
Lehmann
Manfred
M
Polenz
Dietrich
D
Pascher
Andreas
A
Volk
Hans-Dieter
HD
Reinke
Petra
P
D000818:Animals; D000906:Antibodies / Q000276:immunology* / Q000627:therapeutic use*; D001835:Body Weight; D015704:CD4 Antigens / Q000276:immunology*; D002470:Cell Survival; D006085:Graft Survival / Q000276:immunology*; D007421:Intestine, Small / Q000276:immunology* / Q000473:pathology / Q000637:transplantation*; D008214:Lymphocytes / Q000166:cytology; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000276:immunology*; D015996:Survival Rate; D013997:Time Factors; D014019:Tissue Donors; D014184:Transplantation, Homologous
D000906:Antibodies; D015704:CD4 Antigens; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I