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High-dose pentoxifylline in patients with AIDS: inhibition of tumor necrosis factor production. National Institute of Allergy and Infectious Diseases AIDS Clinical Trials Group.

Abstract
Tumor necrosis factor-alpha (TNF) may activate human immunodeficiency virus (HIV), antagonize zidovudine activity, and contribute to AIDS wasting syndrome. Pentoxifylline decreases TNF production. In cell culture, pentoxifylline decreases HIV replication and gene expression. Since an AIDS Clinical Trial Group study suggested that pentoxifylline (400 mg thrice daily) is safe in AIDS patients and decreases TNF mRNA levels in peripheral blood mononuclear cells (PBMC), a second cohort received 800 mg thrice daily for 8 weeks. During treatment, the median decrease in TNF production by PBMC cultured with 0.1 microgram/mL lipopolysaccharide (LPS) was 40%. The median change in TNF mRNA was a 34% decrease. Pentoxifylline did not affect HIV levels as detected by quantitative microculture or serum p24 antigen measurements, nor did it alter zidovudine pharmacokinetics. The most common toxicity was gastrointestinal. Pentoxifylline at dosages of less than thrice-daily 800 mg is well tolerated and may decrease TNF mRNA levels and LPS-induced TNF production.
AuthorsB J Dezube, M M Lederman, J G Spritzler, B Chapman, J A Korvick, C Flexner, S Dando, M R Mattiacci, C M Ahlers, L Zhang
JournalThe Journal of infectious diseases (J Infect Dis) Vol. 171 Issue 6 Pg. 1628-32 (Jun 1995) ISSN: 0022-1899 [Print] United States
PMID7769305 (Publication Type: Clinical Trial, Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • RNA, Messenger
  • Triglycerides
  • Tumor Necrosis Factor-alpha
  • beta 2-Microglobulin
  • Biopterin
  • Neopterin
  • Pentoxifylline
Topics
  • Acquired Immunodeficiency Syndrome (drug therapy)
  • Biopterin (analogs & derivatives, blood)
  • Body Weight (drug effects)
  • CD4 Lymphocyte Count
  • Drug Therapy, Combination
  • Gene Expression (drug effects)
  • Humans
  • Neopterin
  • Pentoxifylline (administration & dosage, pharmacokinetics, toxicity)
  • RNA, Messenger (genetics)
  • Triglycerides (blood)
  • Tumor Necrosis Factor-alpha (biosynthesis, genetics)
  • beta 2-Microglobulin (metabolism)

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