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.
Roilides
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Infectious Diseases Section, National Cancer Institute, Bethesda, Maryland 20892.
Venzon
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Pizzo
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Rubin
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D002470:Cell Survival / Q000187:drug effects; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016049:Didanosine / Q000097:blood / Q000494:pharmacology*; D015658:HIV Infections / Q000097:blood / Q000188:drug therapy; D015497:HIV-1; D006801:Humans; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D010587:Phagocytosis / Q000187:drug effects; D013481:Superoxides / Q000378:metabolism; D016047:Zalcitabine / Q000097:blood / Q000494:pharmacology*; D015215:Zidovudine / Q000097:blood / Q000494:pharmacology*
D013481:Superoxides; D015215:Zidovudine; D016047:Zalcitabine; D016049:Didanosine