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

  • 1 January 1990
    • journal article
    • research article
    • Vol. 75  (1) , 40-47
Abstract
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 a 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 < .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 times 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 an 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 < .01). This suppression of IL-1.beta. and TNF by IL-6 appears to be on the level of transcription.

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