149 research outputs found
Activation of PPARgamma enhances in vitro the immunosuppressive effect of cyclosporine on T lymphocytes.
Background: Peroxisome Proliferator-Activated Receptor gamma (PPAR gamma) is a nuclear receptor that regulates the transcription of genes associated with lipid and glucose metabolism. Recently, it has been shown that PPAR gamma modulates the activity of T cells, resulting in inhibition of T cell proliferation and IL-2 release. In this study we investigated whether the PPAR gamma ligand rosiglitazone (R) enhances in vitro the immunosuppressive effects of cyclosporine A (CsA).
Methods: CD4(+) T cells isolated from peripheral blood mononuclear cells of healthy donors were activated either with mitogens or by one-way mixed lymphocyte reaction. The activated T cells were treated with (1) CsA at low and high concentration (50, 150 ng/ml); (2) R (20 mu M); (3) R (20 mu M) in combination with CsA at low concentration (50 ng/ml). We studied the effects of the various treatments on cell proliferation (incorporation of [H-3] thymidine), the cell-cycle phases (FACS analysis), IL-2 release (ELISA), and IL-2 receptor (CD25) expression (FACS analysis).
Results: R used alone reduced T cell proliferation and CD25 expression. Low-dose CsA combined with R was significantly more powerful than either high-dose CsA alone or R alone in suppressing IL-2 release, arresting the T cell cycle, and blocking the growth of activated T cells.
Conclusion: PPAR gamma ligand R potentiates in vitro the inhibitory action of CsA on activated T helper cells. The combined use of PPAR gamma ligands and low-dose CsA represents a rationale therapeutic approach aimed to prevent CsA nephrotoxicity while maintaining adequate immunosuppression. (C) 2007 Elsevier B.V. All rights reserved.
Accession Number: WOS:00024799570000
Loop diuretics and renal vasodilators in acute renal failure
Loop diuretics are powerful drugs able to increase urinary sodium and water excretion even in conditions of marked impairment of renal function. Loop diuretics are useful in preventing or ameliorating the course of acute renal failure. This effect may be obtained when they are used within 18 h after the ischaemic and/or toxic event. Loop diuretics reduce tubular work, providing resistance to cellular ischaemia. Other important beneficial effects include tubular wash-out of cellular debris and inhibition of tubuloglomerular feedback. Among vasodilators, dopamine, when used at 'dopaminergic dosage' is useful in preventing acute renal failure. Its efficacy is demonstrated in several situations of renal hypoperfusion, i.e. salt depletion, cyclosporin administration, and therapy with recombinant interleukin 2 in cancer patients. According to our studies it appears that dopamine should be used in the early phases of acute renal failure to improve renal perfusion, re-establish glomerular filtration rate, and increase tubular flow
Circulating serum lectins of patients with IgA nephropathy stimulate IL-6 release from mesangial cells.
IF = 7.4
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