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



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



European Journal of Immunology 19(9): 1531-1536



Cell-associated and secreted interleukin 1.alpha. (IL 1.alpha.), IL 1.beta. and tumor necrosis factor .alpha. (TNF-.alpha.), 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 1.alpha. in medium containing 1% heat-inactivated serum was two-to-three times higher than IL 1.beta. However, in the presence of 1% serum and 5% fresh plasma, IL 1.alpha. and IL 1.beta. were produced in similar amounts. Independent of the culture conditions, 90% of the IL 1.alpha. remained cell associated whereas 80% of IL 1.beta. was extracellular. The kinetics of production and release of IL 1.alpha., .beta. and TNF-.alpha. were also studied. IL 1.alpha. and TNF-.alpha. reached maximal levels within 6 h of stimulation, whereas IL 1.beta. reached maximal levels between 12 and 16 h. IL 1.alpha. remained primarily cell associated (80%) for the first 24 h. After 48 h, extracellular IL 1.alpha. exceeded cell-associated levels. IL 1.beta. was primarily secreted (80%), appearing the extracellular fluid within 6 h. TNF-.alpha. 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 1.alpha. is predominantly a cell-associated cytokine acting on a cell-cell basis, whereas IL 1.beta. and TNF-.alpha. are secreted as paracrine mediators.

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Accession: 007207313

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PMID: 2792179

DOI: 10.1002/eji.1830190903


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