Aspirin Promotes Kidney Allograft Survival and Function

Abstract

We read with interest the article by Grotz et al. describing the remarkable finding that aspirin is associated with improved allograft function and prolonged allograft survival after kidney transplantation (1). The results of the retrospective multivariate analysis indicate that low-dose aspirin was a highly significant and independent determinant of improved graft survival (relative risk 0.44; P<0.0001) and function (1). In agreement with the prevailing view of aspirin acting primarily on platelets through cyclooxygenase inhibition, the authors speculate that aspirin’s beneficial effects in kidney transplantation are due to platelet inhibition and subsequent deceleration of transplant vasculopathy. We wish to add that there is an increasing body of evidence indicating that aspirin targets dendritic cell maturation and function (2–4). Dendritic cells are uniquely well-equipped antigen presenting cells that initiate and regulate immune responses. We and others recently reported that aspirin profoundly inhibited CD40, CD80, CD86, and MHC class II expression on bone marrow-derived dendritic cells (2, 3, 5). Aspirin-exposed dendritic cells were poor stimulators of T-cell proliferation and induced lower levels of interleukin-2 in responding T cells (2, 3). Furthermore, investigation of the in vivo function of aspirin-treated dendritic cells revealed an inability to induce normal cell-mediated contact hypersensitivity (2). Further experiments indicated that these effects were cyclooxygenase independent and were related to the suppression of the transcription factor NF-κ B (2, 3). Although these experiments were performed at concentrations exceeding those achievable after low-dose aspirin therapy (81–100 mg/day), they provided evidence that the most commonly used analgesic and anti-inflammatory agent aspirin targets key functions of dendritic cells. If we bear in mind that kidney transplant recipients are taking aspirin in combination with other immunosuppressive agents for several years, we suggest an alternative hypothesis that the “wonder drug” aspirin might promote allograft survival because of its effects on dendritic cells, nature’s adjuvants in the initiation of antigen-specific immune responses. We entirely agree that further studies revealing aspirin’s potential in organ transplantation are desirable. H. Hackstein Institute for Clinical Immunology and Transfusion Medicine Justus-Liebig University Giessen Giessen, Germany R. Shapiro A.W. Thomson Thomas E. Starzl Transplantation Institute Department of Surgery University of Pittsburgh Pittsburgh, Pennsylvania