Tolerance to endotoxin (lipopolysaccharide, LPS) was shown to be mediated by an inhibition of cytokine production. We have studied the effect of 3-day pretreatment with LPS on production of IL-6 in response to a subsequent challenge with LPS in a mouse glioma. The results indicated that in this model, a complete blockade of IL-6 production is induced by LPS pretreatment. This is associated with a decrease of LPS-induced IL-6 mRNA levels. LPS- induced IL-6 production can be restored by PMA, as it was previously observed in vivo, suggesting that down-regulation of IL-6 response in LPS tolerance occurs at the transcriptional level, probably by down-regulating protein kinase C or some other PMA-activable signaling system. IL-6 production is also down-regulated by 3-day preincubation with IL-6 and, to a lesser extent, with IL-1 or TNF, indicating that IL-6 can down-regulate its own production.
|Number of pages||5|
|Journal||Lymphokine and Cytokine Research|
|Publication status||Published - 1993|
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