TY - JOUR
T1 - Early down-regulation of TNF production by LPS tolerance in human monocytes
T2 - Comparison with IL-1β, IL-6, and IL-8
AU - Mengozzi, M.
AU - Fantuzzi, G.
AU - Sironi, M.
AU - Bianchi, M.
AU - Fratelli, M.
AU - Peri, G.
AU - Bernasconi, S.
AU - Ghezzi, P.
PY - 1993
Y1 - 1993
N2 - We studied the effect of a 4-hr preexposure to LPS on the ability of human monocytes to respond to a subsequent stimulation with LPS in terms of cytokine production. LPS-preexposed monocytes did not produce TNF on LPS restimulation, but they retained the ability to produce IL-1β, IL-6, and IL- 8. LPS-tolerant monocytes were still capable of producing TNF when restimulated with zymosan. Down-regulation of TNF by LPS tolerance was also evident at the mRNA level. To investigate the possible mechanisms underlying this phenomenon, we also studied the effect of LPS preexposure on membrane CD14, which was suggested to be an LPS receptor, and on intracellular cAMP, an inhibitor of TNF production. LPS induced a 50% decrease in CD14 expression. On the other hand, the increase in cAMP levels by LPS was not affected by preexposure to LPS. In conclusion, (a) TNF is more rapidly down- regulated than IL-1β, IL-6, and IL-8 during LPS tolerance in vitro; (b) early LPS tolerance is associated with decreased CD14, which might partially explain the decreased LPS response; and (c) a feedback mechanism controlling TNF synthesis, cAMP elevation, is not down-regulated in LPS tolerance.
AB - We studied the effect of a 4-hr preexposure to LPS on the ability of human monocytes to respond to a subsequent stimulation with LPS in terms of cytokine production. LPS-preexposed monocytes did not produce TNF on LPS restimulation, but they retained the ability to produce IL-1β, IL-6, and IL- 8. LPS-tolerant monocytes were still capable of producing TNF when restimulated with zymosan. Down-regulation of TNF by LPS tolerance was also evident at the mRNA level. To investigate the possible mechanisms underlying this phenomenon, we also studied the effect of LPS preexposure on membrane CD14, which was suggested to be an LPS receptor, and on intracellular cAMP, an inhibitor of TNF production. LPS induced a 50% decrease in CD14 expression. On the other hand, the increase in cAMP levels by LPS was not affected by preexposure to LPS. In conclusion, (a) TNF is more rapidly down- regulated than IL-1β, IL-6, and IL-8 during LPS tolerance in vitro; (b) early LPS tolerance is associated with decreased CD14, which might partially explain the decreased LPS response; and (c) a feedback mechanism controlling TNF synthesis, cAMP elevation, is not down-regulated in LPS tolerance.
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M3 - Article
C2 - 7692988
AN - SCOPUS:0027164726
VL - 12
SP - 231
EP - 236
JO - Lymphokine and Cytokine Research
JF - Lymphokine and Cytokine Research
SN - 0277-6766
IS - 4
ER -