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Correlations and interactions in the production of interleukin-6 (IL- 6),
IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells:
IL-6 suppresses IL-1 and TNF
R Schindler, J Mancilla, S Endres, R Ghorbani, SC Clark and CA Dinarello
Department of Medicine, Tufts University School of Medicine, Boston, MA.
Interleukin-6 (IL-6) shares several biologic properties with IL-1,
including hematopoietin-1 activity and stimulation of T cells. Because many
of their biologic activities overlap, we developed and used a specific
radioimmunoassay (RIA) for IL-6 to compare production of this cytokine on a
molar basis with that of IL-1 alpha, IL-1 beta, and tumor necrosis factor
(TNF)alpha. The RIA correlated well with the hybridoma bioassay for IL-6 (r
= .87, P less than .001). Freshly isolated human peripheral blood
mononuclear cells (PBMC) cultured in the absence of stimuli did not produce
IL-6 in most cases. Kinetics of secretion and cell-association of IL-6 were
studied. In contrast to IL-1 alpha but similar to TNF, IL-6 was almost
entirely secreted into the extracellular fluid. Incubation with different
stimuli (lipopolysaccharide [LPS], phytohemagglutinin [PHA], Staphylococcus
epidermidis, or IL-1 alpha) resulted in production of IL-6. However, on a
molar basis PBMC produced approximately two to three times less IL-6 than
IL-1 alpha, IL-1 beta, or TNF, regardless of the stimulus. The amount of
IL-6 produced from PBMC was consistent when measured in the same subjects
six time during a 12-week period. In a cohort of 38 donors, the coefficient
of variation for IL-6 production was .32, compared with .92 for IL-1 beta
and .96 for TNF. Comparing cytokine production by PBMC, there was a
significant correlation between IL-6 and IL-1 beta (r = .72) and between
IL-6 and TNF (r = .66). IL-6 did not stimulate IL-1 beta or TNF production,
but suppressed IL-1 beta and TNF production induced by LPS or PHA by 30% (P
less than .01). This suppression of IL-1 beta and TNF by IL-6 appears to be
on the level of transcription.
Volume 75,
Issue 1,
pp. 40-47,
01/01/1990
Copyright © 1990 by The American Society of Hematology
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