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Subcutaneous administration of a neutralizing IL ‐1β antibody prolongs limb allograft survival
Author(s) -
Hautz Theresa,
Grahammer Johanna,
Moser Dominik,
Eberhart Nadine,
Zelger Bettina,
Zelger Bernhard,
Blumer Michael J.,
Drasche Astrid,
Wolfram Dolores,
Troppmair Jakob,
Öfner Dietmar,
Schneeberger Stefan
Publication year - 2018
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.14765
Subject(s) - medicine , neutralizing antibody , administration (probate law) , antibody , immunology , political science , law
Cytokine‐expression profiles revealed IL ‐1ß highly upregulated in rejecting skin of limb allografts. We investigate the effect of intragraft treatment with a neutralizing IL ‐1β antibody in limb transplantation. Following allogenic hind‐limb transplantation, Lewis rats were either left untreated[1][Shores JT, 2015] or treated with anti‐lymphocyte serum + tacrolimus (baseline)[2][Kanitakis J, 2003]; baseline immunosuppression + anti‐ IL ‐1β (1 mg/kg once/week, 6‐8 subcutaneous injections) into the transplanted[3][Wolfram D, 2015] or contralateral[4][Wolfram D, 2014] limb. Endpoint was rejection grade III or day 100. Graft rejection was assessed by histology, immunohistochemistry, flow cytometry phenotyping of immune cells, and monitoring cytokine expression. Anti‐ IL ‐1β injections into the allograft or contralateral limb resulted in a significant delay of rejection onset (controls: 58.60 ± 0.60; group 3: 75.80 ± 10.87, P = .044; group 4: 73.00 ± 6.49, P = .008) and prolongation of graft survival (controls: 64.60 ± 0.87; group 3: 86.60 ± 5.33, P = .002; group 4: 93.20 ± 3.82, P = .002), compared to controls. Although the phenotype of the graft infiltrating immune cells did not differ between groups, significantly decreased skin protein levels of IL ‐1β, IL ‐4, IL ‐13, IP ‐10, MCP ‐1, and MCP ‐3 in long‐term‐survivors indicate an overall decrease of chemoattraction and infiltration of immune cells as the immunosuppressive mechanism of anti‐ IL ‐1β. Inhibition of IL ‐1β with short‐term systemic immunosuppression prolongs limb allograft survival and represents a promising target for immunosuppression in extremity transplantation.