THE MAXIMAL TOLERABLE INTRAVENOUS DOSAGE OF PENTOXIFYLLINE IN AIDS PATIENTS DOES NOT INHIBIT LIPOPOLYSACCHARIDE-STIMULATED TUMOR-NECROSIS-FACTOR-ALPHA PRODUCTION

Tumor necrosis factor alpha (TNF-alpha) may be involved in the pathoge nesis of metabolic and endocrine changes in HIV infection, Pentoxifyll ine (PTX) is able to suppress the production of TNF-alpha in vitro. Th e effect of two dosages of intravenously administered PTX on clinical symptoms and ex vivo LPS-stimulated TNF-alpha 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 necessita ted termination of infusion after 30 min, The average plasma concentra tion 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 report ed to suppress TNF-alpha production in vitro, No effect of PTX infusio n (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, UPS-stimulated ex vivo TNF-alpha production, at the LPS concentrations tested, was not inhibited by the plasma conc entration of PTX that could be achieved at this dosage.