Effects of antiretroviral dideoxynucleosides on polymorphonuclear leukocyte function.

Abstract

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.

• Authors: E Roilides, D Venzon, P A Pizzo, M Rubin
• Journal: Antimicrobial agents and chemotherapy (Antimicrob Agents Chemother) Vol. 34 Issue 9 Pg. 1672-7 (Sep 1990) ISSN: 0066-4804 [Print] United States
• PMID: 2178334 (Publication Type: Clinical Trial, Comparative Study, Controlled Clinical Trial, Journal Article)

Chemical References

• Superoxides
• Zidovudine
• Zalcitabine
• Didanosine

Topics

• 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)