cytokineinduced il1 beta gene expression in the human polymorphonuclear leukocyte transcriptional and posttranscriptional regulation by tumor necrosis factor and il1 we have previously demonstrated that il1 and tnf could rapidly but transiently induce gene expression of il1 beta in human polymorphonuclear leukocytes pmn at both the protein and mrna level additionally we demonstrated a cooperative effect of il1 and tnf on the kinetics of induction of il1 beta mrna and protein in order to better understand the molecular basis of il1 beta induction we have further investigated the regulation of il1 and tnfinduced gene expression in the pmn using nuclear runon transcription analysis we found that within 1 h il1 tnf and tnf plus il1 induced the transcription of the il1 beta gene by 33 61 and 99fold respectively by 2 h the levels of transcription had been reduced to approximately 50 of peak levels for tnf and tnf plus il1treated pmn and to near noninduced levels in il1treated pmn we also found that these cytokines induced stable mrna ie il1 beta mrna t12 for il1 tnf and tnf plus il1induced pmn were 57 94 and 86 min respectively by 2 h when steady state levels of il1 beta mrna were found to decrease il1 beta mrna t12 had fallen to approximately 18 min for all cytokine treatments to determine if protein synthesis was required for induction of il1 beta gene expression we treated pmn simultaneously with cytokines and cycloheximide and found that cycloheximide enhanced the accumulation of il1induced il1 beta mrna but abrogated the accumulation of il1 beta mrna by tnf or tnf plus il1treated pmn this abrogation of il1 beta mrna accumulation was not caused by inhibition of induction of il1 beta transcription because tnf induction of transcription of il1 beta was not affected by simultaneous treatment with cycloheximide thus we report that il1 and tnf regulate il1 beta gene expression via both transcriptional and posttranscriptional mechanisms in vitro