TY - JOUR
T1 - Correlations and interactions in the production of interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF) in human blood mononuclear cells
T2 - IL-6 suppresses IL-1 and TNF
AU - Schindler, R.
AU - Mancilla, J.
AU - Endres, S.
AU - Ghorbani, R.
AU - Clark, S. C.
AU - Dinarello, C. A.
PY - 1990
Y1 - 1990
N2 - 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-1α, IL-1β, and tumor necrosis factor (TNF)α. 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-1α 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-1α) resulted in production of IL-6. However, on a molar basis PBMC produced approximately two to three times less IL-6 than IL-1α, IL-1β, 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-1β and .96 for TNF. Comparing cytokine production by PBMC, there was a significant correlation between IL-6 and IL-1β (r = .72) and between IL-6 and TNF (r = .66). IL-6 did not stimulate IL-1β or TNF production, but suppressed IL-1β and TNF production induced by LPS or PHA by 30% (P < .01). This suppression of IL-1β and TNF by IL-6 appears to be on the level of transcription.
AB - 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-1α, IL-1β, and tumor necrosis factor (TNF)α. 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-1α 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-1α) resulted in production of IL-6. However, on a molar basis PBMC produced approximately two to three times less IL-6 than IL-1α, IL-1β, 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-1β and .96 for TNF. Comparing cytokine production by PBMC, there was a significant correlation between IL-6 and IL-1β (r = .72) and between IL-6 and TNF (r = .66). IL-6 did not stimulate IL-1β or TNF production, but suppressed IL-1β and TNF production induced by LPS or PHA by 30% (P < .01). This suppression of IL-1β and TNF by IL-6 appears to be on the level of transcription.
UR - http://www.scopus.com/inward/record.url?scp=0025176658&partnerID=8YFLogxK
U2 - 10.1182/blood.v75.1.40.bloodjournal75140
DO - 10.1182/blood.v75.1.40.bloodjournal75140
M3 - Artículo
SN - 0006-4971
VL - 75
SP - 40
EP - 47
JO - Blood
JF - Blood
IS - 1
ER -