KINETICS OF IL1-BETA MESSENGER-RNA AND PROTEIN ACCUMULATION IN HUMAN MONONUCLEAR-CELLS

Interleukin 1 beta (IL1-beta) is an inducible polypeptide with many roles in host defence and homoeostasis. It has also been implicated as a mediator of infectious, inflammatory and autoimmune diseases, and the kinetics of its production are relevant to an understanding of the pathogenesis of these conditions. We report here the time-course of IL1-beta production in human adherent monocytes. Both IL1-beta protein and mRNA were measured following cell activation with bacterial endotoxin (lipopolysaccharide; LPS), and pro-inflammatory crystals of monosodium urate (MSU), which cause arthritis and kidney disease. We also tested other crystal types associated with arthritis, namely hydroxylapatite and calcium pyrophosphate dihydrate. IL1 was absent from unstimulated cells, but IL1-beta mRNA accumulated rapidly after LPS or MSU stimulation and was associated with the later appearance of intracellular IL1-beta protein which was subsequently released from the cells (60% at 9 h). The other crystals failed to induce significant IL1 production. Our findings support the view that production of IL1-beta in human mononuclear cells is based on rapid translation of an inducible pool of mRNA and that no pre-formed mRNA or intracellular protein exists in normal blood monocytes. Further, although IL1-beta is translated without a conventional leader sequence, it is translocated extracellularly with the kinetics of a secretory protein.