Activin Inhibition Reduces Early Injury After Kidney Transplantation.

Abstract

INTRODUCTION The innate immune response augments adaptive immunity and may also trigger repair processes that lead to uncontrolled fibrosis and atherosclerosis as seen in chronic allograft injury. The activins are members of the transforming growth factor β superfamily. They play critical roles in the onset of acute and chronic inflammatory conditions such as septicemia, asthma, and fibrosis. The role of activins in transplantation is unknown. In this study we investigated how activin inhibition affects early inflammation after kidney transplantation. METHODS A rat renal transplantation model was used. Activin A and B signaling was inhibited with a soluble activin receptor ActRIIB-Fc. In the study group ActRIIB-Fc was given to the transplant recipient i.p. two hours before the transplantation (n=5). In addition transplant recipients were treated daily with cyclosporine A (CsA) 1.5 mg/kg s.c. The control group received CsA only (n=5). Rats were followed for 72 hours. Immunohistochemical stainings were used to detect different inflammatory cell populations in the kidney transplants. RESULTS Activin inhibition significantly decreased the number of ED3+ macrophages (control vs. treatment: 50±13 vs. 16±4 cells/mm2, p<0.05), MPO+ neutrophiles (26±5 vs.10±2 cells/mm2, p<0.05) and OX62+ dendritic cells (24±8 vs. 11±6 cells/mm2, p<0.05) in the kidney transplants 72 hours after transplantation. ActRIIB-Fc did not affect CD4+ or CD8+ T cell infiltration. CONCLUSIONS Activin inhibition efficiently decreses the infiltration of macrophages, dendritic cells and neutrophilic cells to the kidney transplant in rat. These cells are characteristic to innate immunity response. The inhibition of innate immunity could be of use in the prevention of kidney allograft injury.