Production of intra- and extracellular interleukin-1 (IL-1) by human monocytes

Human monocytes, separated by adherence and cultured in plastic wells, produced "spontaneously" high levels of intracellular interleukin-1 (IL-1) during the first 20 hr in culture while releasing in most cases less than 10% of it into the medium. The addition of bacterial lipopolysaccharides (LPS), quartz silica particles, zymosan, or phorbol myristate acetate (PMA) enhanced 3 to 50 times the overall production and 25 to 2000 times the release of IL-1. From 24 to 44 hr of culture, the "spontaneous" production and release of IL-1 decreased to negligible amounts. During the same period of time, the addition of silica particles or PMA had clearly less effect while the addition of LPS or zymosan produced high levels of intracellular IL-1 but only a modest release of it. When any of the stimuli was added after the first 48 hr and up to 6 days of culture, no release of IL-1 was detected and only a small amount of the intracellular fraction was seen when using LPS or zymosan. These results were not due to cell death prior to the addition of the stimuli but rather to a decrease in the responsiveness of the mononuclear phagocytes that coincides with their transformation into macrophages. The different patterns of production and release observed with time suggest that synthesis and secretion of IL-1 by human monocytes are two distinct biological events.