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.
ASJC Scopus subject areas
- Immunology and Allergy