IN VIVO EXPRESSION OF TRANSFORMING GROWTH FACTOR-??1 IN HUMANS

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Abstract
Background. Transforming growth factor-β1(TGF-β1) is an immunoregulatory and fibrogenic cytokine. In an earlier in vitro study, we demonstrated that cyclosporine (CsA) increases TGF-β1transcription rate in human T lymphocytes. Herein, we explored whether CsA augments the in vivo expression of TGF-β1in humans. Methods. The inherent difficulty in studying the in vivo effect of CsA in humans was circumvented by investigating stable end-stage renal disease patients who were preconditioned with CsA before their living donor renal transplantation. Sera and peripheral blood mononuclear cells were obtained from CsA-preconditioned patients and quantified for TGF-β1expression at the mRNA (by competitive polymerase chain reaction) and protein (sandwich enzyme-linked immunosorbent assay) levels. Results. Our studies demonstrated a significant increase in TGF-β1expression after CsA therapy. The stimulatory effect was unique to TGF-β1, and CsA did not increase interleukin (IL)-10, IL-6, IL-2, or tumor necrosis factor-α expression. Conclusions. Our first-time demonstration of a TGF-β1-selective in vivo stimulatory effect of CsA in humans: (1) advances a TGF-β1-centered hypothesis for the beneficial(immunosuppression) and detrimental (fibrosis, hypertension) effects of CsA use, and (2) broadens the mechanism of immunosuppressive action of CsA to include heightened expression of an endogenous immunosuppressive cytokine.