Zidovudine inhibits functional extracellular monocytic interleukin-1.
Zidovudine (AZT) penetrates human monocytes to exert its antiretroviral activity at the level of reverse transcriptase in infected cells. Stimulation of normal human monocytes with lipopolysaccharide (LPS) results in the transcription of interleukin-1 (IL-1) genes, the intracellular accumulation of IL-1 alpha and IL-1 beta precursors, and the subsequent extracellular release of functional IL-1 beta. The present study demonstrates that zidovudine inhibits the extracellular release of IL-1 activity without affecting the generation of intracellular IL-1 or the amount of released IL-1 beta protein. Similar results were observed with monocytes from normal individuals and monocytes from patients with AIDS. Since IL-1 may upregulate the expression of HIV genes in infected cells, the inhibitory effect of zidovudine on the release of functional IL-1 may be relevant for the beneficial effect of the drug in HIV infection.
Weiss
L
L
Unité d'Immunopathologie, INSERM U28, Hôpital Broussais, Paris, France.
Haeffner-Cavaillon
N
N
Gilquin
J
J
Kazatchkine
M D
MD
D005110:Extracellular Space / Q000276:immunology; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis / Q000378:metabolism*; D007424:Intracellular Fluid / Q000276:immunology; D009000:Monocytes / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D015215:Zidovudine / Q000494:pharmacology*
D007375:Interleukin-1; D015215:Zidovudine