The Maximal Tolerable Intravenous Dosage of Pentoxifylline in AIDS Patients Does Not Inhibit Lipopolysaccharide-Stimulated Tumor Necrosis Factor α Production

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Abstract
Tumor necrosis factor α (TNF-α) may be involved in the pathogenesis of metabolic and endocrine changes in HIV infection. Pentoxifylline (PTX) is able to suppress the production of TNF-α in vitro. The effect of two dosages of intravenously administered PTX on clinical symptoms and ex vivo LPS-stimulated TNF-α production was evaluated in six clinically stable AIDS patients in a saline-controlled study. PTX in a dosage of 1.5 mg/min was tolerated without side effects. PTX in a dosage of 2.1 mg/min resulted in intolerable nausea and necessitated termination of infusion after 30 min. The average plasma concentration of PTX after infusion of 1.5 mg/min for 6 hr was 510 ± 56 ng/ml, which is considerably below the concentrations that have been reported to suppress TNF-α production in vitro. No effect of PTX infusion (1.5 mg/min) on LPS-stimulated TNF production ex vivo was found. Our conclusion is that the maximally tolerated i.v. dosage of PTX in AIDS patients is 1.5 mg/min. LPS-stimulated ex vivo TNF-α production, at the LPS concentrations tested, was not inhibited by the plasma concentration of PTX that could be achieved at this dosage.