Patterns and Sites of Tumor Necrosis Factor-α and Transforming Growth Factor-β1 Expression in Human Renal Allograft Biopsies

Abstract

The immune system is regulated by the release of cytokines which influence cellular activation, differentiation and function.1 Cytokines play a major role in inflammatory and immune responses that mediate allorecognition and rejection.2 A number of cytokines have been implicated in these responses. Tumor necrosis factor (TNF)-α a lymphocyte- and macrophage-derived cytokine with pleiotrophic actions, exerts proinflammatory functions that may play an important role in initiating the rejection response. There is an evidence for increased production of TNF-α among patients undergoing acute cellular rejection after transplantation based upon measurements of both serum levels and intragraft messenger RNA.³-⁴ Chronic allograft nephropathy, a relentlessly progressive process is a major cause of long-term graft dysfunction and ultimate failure. Given the prominent role of transforming growth factor (TGF)-β1 in tissue repair and in fibrosis, it is believed that intragraft levels of this cytokine are related to chronic allograft nephropathy. The pro-fibrotic effect of this cytokine include increased collagen production, decreased proteolytic enzyme content (eg, collagenase), and augmented protease inhibitor synthesis (eg, plasminogen activator inhibitor).5 Although elevated levels of TNF-α and TGF-β1 have been implicated in renal allograft rejection, the tissue distribution and cellular localization of cytokines during this process is not entirely clear.6 In this study, we evaluated the expression (sites and patterns of expression) of TNF-α and TGF-β1 by immunohistochemistry and in situ hybridization.