Treatment with keratinocyte growth factor does not improve lung allograft survival in the rat.
OBJECTIVE
Lung allografts are threatened by primary graft dysfunction, infections, and rejection. Novel therapies protecting pulmonary allografts are badly needed. Keratinocyte growth factor (KGF) protects the lung against a variety of injurious stimuli and exerts anti-inflammatory effects. The aim of the study was to test the potential of recombinant truncated KGF (DeltaN23-KGF, palifermin) to attenuate pulmonary allograft rejection.


METHODS
Intratracheal instillation of 5 mg/kg DeltaN23-KGF was performed twice in donor rats on days 3 and 2 before explantation of the lung. In control animals, an equivalent volume of vehicle was instilled. Left lungs were transplanted in the fully allogeneic Dark Agouti to Lewis rat strain combination and in the less stringent Fischer 344 to Wistar Kyoto combination. Allograft recipients were additionally treated with DeltaN23-KGF post-transplantation. Graft outcome, leukocytic infiltration, and major histocompatibility complex (MHC) class II antigen expression was analyzed.


RESULTS
In both rat strain combinations, DeltaN23-KGF treatment did not improve pulmonary allograft outcome. Graft infiltration by macrophages and T lymphocytes remained unchanged. In addition, we demonstrated that MHC class II antigens were more abundant in KGF-treated allografts compared to control-treated grafts, which probably results in an increased alloreactivity.


CONCLUSIONS
In conclusion, intratracheal DeltaN23-KGF treatment is not effective to prevent acute pulmonary allograft rejection.
Hirschburger
Markus
M
Laboratory of Experimental Surgery, Department of General and Thoracic Surgery, University of Giessen Lung Center, Justus-Liebig-University Giessen, Rudolf-Buchheim-Str. 7, 35385, Giessen, Germany.
Obert
Martin
M
Traupe
Horst
H
Kuchenbuch
Tim
T
Padberg
Winfried
W
Fehrenbach
Heinz
H
Grau
Veronika
V
D000818:Animals; D051523:Fibroblast Growth Factor 7 / Q000494:pharmacology*; D006084:Graft Rejection / Q000473:pathology; D006085:Graft Survival / Q000187:drug effects*; D000949:Histocompatibility Antigens Class II / Q000032:analysis; D007124:Immunoenzyme Techniques; D008168:Lung / Q000187:drug effects / Q000473:pathology; D016040:Lung Transplantation / Q000473:pathology*; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D011917:Rats, Inbred Lew; D011919:Rats, Inbred Strains; D011921:Rats, Inbred WKY; D011994:Recombinant Proteins / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects; D014184:Transplantation, Homologous
D000949:Histocompatibility Antigens Class II; D011994:Recombinant Proteins; D051523:Fibroblast Growth Factor 7