Promyelocytic HL-60 cells differentiated to a neutrophilic phenotype by incubation with all-trans retinoic acid become constitutively apoptotic. Exposure to either LPS or IL-1 beta inhibited the apoptosis of differentiated HL-60 cells. LPS induced the expression of pro-IL-1 beta message, upregulated the activity of the interleukin-1 beta converting enzyme (caspase-1), and increased the release of IL-1 beta into the culture medium. Prevention of IL-1 beta translation with an anti-sense oligonucleotide, or prevention of IL-1 beta cellular binding with a blocking antibody, accelerated rates of spontaneous apoptosis, and abrogated the inhibitory effects of LPS. However inhibition of caspase-1 activity further inhibited constitutive apoptosis of mature HL-60 cells. These studies provide further evidence of a complex regulatory pathway that modulates the expression of granulocyte apoptosis during inflammation, and point to a specific role for IL-1 beta as an autocrine survival factor. (C) 2008 Published by Elsevier Inc.