Differences in the synthesis and kinetics of release of interleukin 1 alpha, interleukin 1 beta and tumor necrosis factor from human mononuclear cells.
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 in the extracellular fluid within 6 h. TNF-alpha appeared in the extracellular fluid within 1 h of incubation, with less than 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.
Lonnemann
G
G
Department of Nephrology, Medizinische Hochschule, Hannover, FRG.
Endres
S
S
Van der Meer
J W
JW
Cannon
J G
JG
Koch
K M
KM
Dinarello
C A
CA
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000378:metabolism*; D007700:Kinetics; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D007375:Interleukin-1; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha