Pentoxiphylline reduces nitric oxide production among patients with HIV infection

Tumour necrosis factor-alpha (TNF-alpha) and nitric oxide (NO) levels are e levated among patients with human immunodeficiency virus (HIV) infection. T NF-alpha is known to lower NO production. In this study we used a TNF-alpha inhibitor, pentoxiphylline, to treat patients with HIV infection who were free of opportunistic infections and see if NO production was altered with this drug. NO production was determined by spectrophotometric analysis usin g nitrite and citrulline as surrogate markers and TNF-c( levels were determ ined by ELISA before and after 4 weeks of the treatment. Nineteen patients (ten males, mean age 36.6 +/- 5.2 years) and 16 age and sex matched healthy controls were studied. Mean CD4 counts of patients were 206.5 mm(3). Nitri te level among patients at recruitment was 99.7 +/- 26.5 nmol/ml (range 50- 167 nmol/ml) and was significantly higher than 46.4 +/- 16.2 nmol/ml; the v alue of healthy controls (P < 0.05). Patient levels declined significantly to 44.2 +/- 19.7 nmol/ml (range 10-106.6 nmol/ml) following 4 weeks of ther apy (P < 0.01). Citrulline level at recruitment was 810.8 +/- 425.8 nmol/ml (range 366.6-1888.7 nmol/ml), which was significantly higher than 488.6 +/ - 224.5 nmol/ml, the level of controls (P ( 0.01). There was a statisticall y significant decrease in these levels among patients to 533.6 +/- 299.5 nm ol/ml (range 250-163.3 nmol/ml) after 4 weeks of therapy (P < 0.01). TNF-al pha levels showed a significant decline in the OD values from 0.34 +/- 0.22 at the start of therapy to 0.24 +/- 0.18 (P < 0.05). We conclude that the use of pentoxiphylline is associated with decrease in TNF-alpha. levels and NO production. (C) 2000 Elsevier Science B.V. All rights reserved.