Abstract
In this study, we investigated the effects of NSAIDs such as indomethacin and d-2- [4- (3-methyl -2-thenyl) phenyl] propionic acid (M-5011), PGE2, cAMP-elevating agents (forskolin, DBcAMP, IBMX) on IL-6 and TNF-α production in PBMC. The effects of NSAIDs on IL -6 production in human monocyte cell line (THP -1 cell) were also studied. NSAIDs downregulated IL-6 production, up-regulated TNF-α production and suppressed PGE2 production in lipopolysaccharide (LPS) -stimulated PBMC. M-5011 down-regulated IL -6 production both at the protein and mRNA levels. The effects of M-5011 on cytokine production was significantly stronger than that of indomethacin, whereas it was opposite on PGE2 production. The inhibition of IL-6 production by NSAIDs were also observed in THP-1 cells, although NSAIDs did not affect PGE2 production from THP-1 cells. PGE2 and CAMP-elevating agents inhibited TNF-α production without affecting IL-6 production in LPS-stimulated PBMC. PGE2, forskolin and DBcAMP induced a dose dependent elevation of the intracellular concentration of cAMP level, but IBMX induced a constant elevation of that. These results suggest that elevation of cAMP is not entirely responsible for regulation of cytokine production, and the downregulation of IL-6 production by NSAIDs may be partly independent of inhibition of PGE2 production.
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