Differences in the synthesis and kinetics of release of interleukin 1α, interleukin 1β and tumor necrosis factor from human mononuclear cells

Abstract

Cell‐associated and secreted interleukin 1α (IL 1α), IL 1β and tumor necrosis factor α (TNF‐α), produced by human mononuclear cells (MNC) in vitro in response to lipopolysaccharide, were measured by radioimmunoassay. After 18 h of incubation, total production of IL 1α in medium containing 1% heat‐inactivated serum was two‐to‐three times higher than IL 1β. However, in the presence of 1% serum and 5% fresh plasma, IL 1α and IL 1β were produced in similar amounts. Independent of the culture conditions, 90% of the IL 1α remained cell associated whereas 80% of IL 1β was extracellular. The kinetics of production and release of IL 1α, β and TNF‐α were also studied. IL 1α and TNF‐α reached maximal levels within 6 h of stimulation, whereas IL 1β reached maximal levels between 12 and 16 h. IL 1α remained primarily cell associated (80%) for the first 24 h. After 48 h, extracellular IL 1α exceeded cell‐associated levels. IL 1β was primarily secreted (80%), appearing in the extracellular fluid within 6 h. TNF‐α appeared in the extracellular fluid within 1 h of incubation, with < 10% cell associated at any time during the 48 h of incubation. Although the three cytokines share many biological activities, this study provides evidence that MNC IL 1α is predominantly a cell‐associated cytokine acting on a cell‐cell basis, whereas IL 1β and TNF‐α are secreted as paracrine mediators.