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Cytokines correlate with age in healthy volunteers, dialysis patients and kidney-transplant patients
Authors:Torsten Bhler  Cindy Canivet  Phuong Ngan Le Nguyen  Sylvain Galvani  Mogens Thomsen  Dominique Durand  Robert Salvayre  Anne Negre-Salvayre  Lionel Rostaing  Nassim Kamar
Institution:aINSERM U. 858 EQ 10, Institut Louis Bugnard, 1 Ave J Poulhès, CHU Rangueil, 3100 Toulouse, France;bDepartment of Nephrology, Dialysis and Multi-Organ Transplantation, CHU Rangueil, Toulouse, France;cGambro Dialysatoren GmbH, Hechingen, Germany
Abstract:T-cell functions are currently used as biomarkers for the pharmacodynamic monitoring of immunosuppressive drugs or as disease biomarkers of inflammation/sepsis and organ rejection. In order to evaluate co-factors potentially influencing the expression of the immunological biomarkers, we explored T-cell proliferation, T-cell activation (CD25 and CD71 expressions) and intra-lymphocyte cytokine production (interleukin (IL)-2 and tumor necrosis factor (TNF)-α) in healthy volunteers, dialysis patients and stable kidney-transplant patients treated with standard immunosuppressive therapy, i.e. tacrolimus, mycophenolic acid with or without steroids. Age was positively correlated with TNF-α expression in all three patient populations, and with IL-2 expression in healthy volunteers and kidney-transplant patients. Further age was correlated with inhibition of lymphocyte proliferation in healthy volunteers and with the T-cell activation marker CD25 in kidney-transplant patients. In healthy volunteers lymphocyte proliferation was higher in woman as compared to men. Other biomarkers of T-cell function were independent of the gender. In the kidney-transplant patient group a significantly lower expression of all biomarkers of T-cell functions compared to healthy volunteers and dialysis patients. In dialysis patients we found significant increased IL-2 expression compared to healthy volunteers, while the other T-cell functions were not significantly different. Further time on dialysis had no effect on the level of biomarker expression. In conclusion we found decreased T-cell functions in kidney-transplant patients compared to healthy volunteers and dialysis patients, increased IL-2 expression in dialysis patients compared to healthy volunteers and in all three populations we found a correlation of age and intra-T-lymphocyte TNF-α expression.
Keywords:Therapeutic drug monitoring  Biomarker  Age  Transplantation  Dialysis
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