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Background. We have studied the effects of interferon (IFN)-γ allelic variations on expression levels of pro- and anti-inflammatory cytokines and on long-term inflammatory status in haemodialysis patients.Methods. Genotyping was performed in 123 patients for single nucleotide polymorphisms in the first intron of the IFN-γ gene (+874 T/A). They were prospectively followed for 2 years. Cytokine mRNA levels in whole blood cells (detected by real time (RT)-PCR technique) and serum C-reactive protein (CRP) concentrations were compared in patient groups with different IFN-γ genotypes. Serum CRP was evaluated every month and inflammatory state was defined as percent of abnormal values (above 5 mg/l) over total determinations. Of the total, 102 patients survived and completed 24±1 monthly CRP determinations. The IFN-γ ±874 A/A, ‘low-producer’ genotype was associated with decreased (P<0.05) mRNA levels of IFN-γ and of interleukin-6 and with a lower (P<0.05) frequency of CRP elevation (37±6%) than the ±874 A/T and T/T, ‘intermediate and high-producer’ genotypes (59±6%, and 60±5%, respectively). The mRNA levels of tumor necrosis factor-α, IL-10 and of transforming growth factor-β1 were not different in the three groups of patients. Pooled analysis in deceased (10±3 monthly CRP determinations) and survived patients confirmed the results obtained in the patients who completed the follow-up period.Conclusions. The ‘low-producer’ IFN-γ +874 A/A genotype was associated with a preventive effect on long-term CRP elevation in haemodialysis patients possibly mediated by decreased gene expression of IFN-γ and IL-6. [ABSTRACT FROM AUTHOR]

Background. Impaired protein anabolism and insulin resistance are characteristic features of maintenance haemodialysis patients. We have used a randomised, matched-paired, double-blind, placebo-controlled experimental design to determine the capability of intravenous l-carnitine supplementation to modify insulin resistance and protein catabolism in non-diabetic patients with end-stage renal disease (ESRD) undergoing chronic haemodialysis treatment. Methods. l-carnitine (20 mg·kg−1) (n = 9) or placebo (n = 10) were given intravenously at the end of seven consecutive dialysis sessions. Whole-body protein and glucose metabolism were assessed on interdialytic days by the L[1-13C]leucine and the [2,2-2H2]glucose kinetic models in the postabsorptive state and during euglicemic hyperinsulinemic clamp studies at baseline and at the end of the treatment period. Results. l-carnitine supplementation was associated with lower (P l-carnitine treatment. Insulin-mediated glucose disappearance was improved by l-carnitine only in those patients (n = 5) (+18 ± 3%, P vs placebo group, n = 5) with greater baseline insulin resistance, selected according to the median value of insulin sensitivity before treatment. Conclusions. l-carnitine supplementation was associated with protein-sparing effects in maintenance haemodialysis patients during hyperinsulinemia. [ABSTRACT FROM AUTHOR]