Open AccessInhibition of TNF‐α reduces transplant arteriosclerosis in a murine aortic transplant model
Author(s) -
Wollin Martina,
Abele Silke,
Bruns Heiko,
Weyand Michael,
Kalden Joachim R.,
Ensminger Stephan M.,
Spriewald Bernd M.
Publication year - 2009
Publication title -
transplant international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.998
H-Index - 82
eISSN - 1432-2277
pISSN - 0934-0874
DOI - 10.1111/j.1432-2277.2008.00802.x
Subject(s) - medicine , infliximab , blockade , tumor necrosis factor alpha , arteriosclerosis , transplantation , monoclonal antibody , antibody , immunology , receptor
Summary Experimental and clinical data provide evidence that TNF‐α contributes to acute and chronic allograft rejection. In this study, we explored the effect of TNF‐α blockade using the chimeric monoclonal antibody infliximab on the development of transplant arterisoclerosis in a fully mismatched aortic allograft model. Post‐transplant treatment of CBA (H2 k ) recipients with 250 μg infliximab (cumulative dose 1.25 mg) reduced luminal occlusion of C57Bl/6 (H2 b ) aortic grafts on day 30 from 77 ± 5% in untreated controls to 52 ± 6%. Increasing the dose of anti‐TNF‐α antibody had no further beneficial effect. Treatment with human control immunoglobulin had no effect on intima proliferation. Under TNF‐α blockade, ICAM‐1 and PDGF mRNA expression within the grafts was strongly reduced, whereas iNOS expression was enhanced. The data show that TNF‐α blockade using infliximab can reduce the development of transplant arteriosclerosis in fully mismatched murine aortic grafts.