Pentoxifylline acutely reduces protein catabolism in chronically uremic patients

Background We investigated the ability of pentoxifylline, a drug with hemorheological actions known to block tumor necrosis factor-alpha (TNF-alpha) release, to modulate whole-body protein kinetics in undialyzed patients with chronic uremia. Methods: Leucine rate of appearance (Ra) from proteolysis and leucine oxidation, a marker of net protein loss, were determined by infusing L-[1-C-13]Ieucine and using the reciprocal pool model for calculations. Results: Intravenous infusion of pentoxifylline in the postabsorptive state (1 mg/kg within 3 hours) decreased the intracellular leucine Ra from proteolysis by -16% +/- 4% versus -3% +/- 2% of saline (P= 0.02) and leucine oxidation by -16% +/- 4% versus +4% +/- 2% of saline (P = 0.003). Combined infusions of pentoxifylline and a balanced amino acid mixture (0.2 mg/kg/min) decreased whole-body proteolysis by -53% +/- 7% versus -26% +/- 6% of amino acid infusion alone (P = 0.02). Circulating levels of TNF-alpha and TNF-alpha soluble receptors (sTNF-Rs) were elevated (P < 0.001) in patients compared with healthy controls. Pentoxifylline infusion did not significantly affect TNF-α levels, but decreased sTNF-Rs both in the postabsorptive state and during hyperaminoacidemia. Conclusion: Pentoxifylline acutely decreased whole-body proteolysis in chronically uremic patients. Potential explanations for these pharmacological effects may include downregulation of the TNF-α system or other mechanisms related to the rheological action of the drug (eg, increased amino acid or insulin delivery to target cells).