Background. The new immunosuppressive drug Rapamycin (Rapa) is endowed with a mechanism of action that is distinct from that of calcineurin inhibitors. It has been claimed that Rapa does not significantly modulate either the cytokine expression or the transcription of several growth factors in mitogen-activated T cells. Previously, we reported that fine-needle aspiration biopsy (FNAB) sample cultures synthesize a large array of cytokines, and some of them may be powerful predictors of acute rejection in renal transplants. We hypothesized that Rapa may induce significant changes on cytokine production by FNAB sample cultures and on serum cytokine receptors when compared to other immunosuppressive drugs.
Flow cytometry study of aspiration biopsy samples of kidney transplant patients is a reliable and powerful method to diagnose acute rejection episodes, although it is needed to consider several lymphocyte phenotypes; cytofluorometric analysis of PBL is important because it provides graft-infiltrating cell to peripheral blood lymphocyte ratios. This safe and rapid test may significantly improve the management of kidney transplant patients.
Cytokine analysis in fine-needle aspiration biopsy cultures supernatants is a very useful immunological screening method for kidney transplants. IL-2 synthesis on day 7 post-transplantation reliably predicted the risk of impending acute rejection during the first weeks. The cytokine pattern suggests that acute rejection is associated with Th1, stable patients with Th0/Th2, and chronic rejection with Th2 patterns.
Monocytes-macrophages are present at higher numbers in aspiration biopsies of kidney transplant patients suffering either acute tubular necrosis or steroid-resistant rejections, but they are present during the first days after transplant in stable patients, too. The production of IL-1ra is significantly up-regulated in stable patients, which suggests that monocytes-macrophages may constitute an early key factor in the down-regulation of the anti-allograft immune response.
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