Effects of antiretroviral dideoxynucleosides on polymorphonuclear leukocyte function.

Dideoxynucleosides (zidovudine[AZT], dideoxycytidine[ddC], and dideoxyinosine[ddI]) are promising new agents for the management of human immunodeficiency virus type 1 (HIV-1) infections. In light of recent data demonstrating defects in the polymorphonuclear leukocyte (PMN) bactericidal activity of HIV-1-infected patients and since many chemotherapeutic agents affect PMN function, we examined their effects on the function of PMNs from both healthy and HIV-1-infected individuals in vitro. AZT (0.1 to 25 microM), ddC (0.01 to 1 microM), and ddI (0.2 to 50 microM) had no effect on viability, chemotaxis to N-fromylmethionyl leucyl phenylalanine, phagocytosis of Candida albicans or Staphylococcus aureus, or superoxide production following stimulation by N-formylmethionyl leucyl phenylalanine. Killing of C. albicans was not affected by AZT but was enhanced by 0.1 and 1 microM ddc (a 1 microM, killing was 26.0 +/- 2.02% compared with 17.0 +/- 0.73% for controls: P = 0.006) and 0.2 to 50 microM ddI (at 10 microM, killing was 25.0 +/- 0.68% compared with 17.8 +/- 0.91% for controls; P = 0.002). Killing of S. aureus was unchanged by AZT and ddC but was significantly enhanced by ddI at 0.2 to 20 microM (at 2 microM, killing was 71.2 +/- 5.57% compared with 51.4 +/- 6.29% for controls; P = 0.0045). In addition, the preexisting defective bactericidal capacity of PMNs from HIV-1-infected patients was enhanced by ddI (P less than 0.025). Potential enhancement by these dideoxynucleosides of certain PMN functions of HIV-1-infected patients deserves further study.
AuthorsE Roilides, D Venzon, P A Pizzo, M Rubin
JournalAntimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 34 Issue 9 Pg. 1672-7 (Sep 1990) ISSN: 0066-4804 [Print] UNITED STATES
PMID2178334 (Publication Type: Clinical Trial, Comparative Study, Controlled Clinical Trial, Journal Article)
Chemical References
  • Superoxides
  • Zidovudine
  • Zalcitabine
  • Didanosine
  • Cell Survival (drug effects)
  • Chemotaxis, Leukocyte (drug effects)
  • Didanosine (blood, pharmacology)
  • HIV Infections (blood, drug therapy)
  • HIV-1
  • Humans
  • Neutrophils (drug effects, immunology, metabolism, physiology)
  • Phagocytosis (drug effects)
  • Superoxides (metabolism)
  • Zalcitabine (blood, pharmacology)
  • Zidovudine (blood, pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!

Choose Username:
Verify Password: