Elsevier

Cytokine

Volume 7, Issue 4, May 1995, Pages 372-379
Cytokine

Regular article
Nonsteroidal anti-inflammatory drugs differentially regulate cytokine production in human lymphocytes : Up-regulation of TNF, IFN-γ and IL-2, in contrast to down-regulation of IL-6 production

https://doi.org/10.1006/cyto.1995.0047Get rights and content

Abstract

Nonsteroidal anti-inflammatory drugs (NSAIDs) are well known as immunoregulators, but the mechanisms of their action are not fully explained by the inhibition of PG synthesis. We have investigated the effect of NSAIDs on cytokine production in human PBMC and T cell clones (TCC). NSAIDs up-regulated TNF, IFN-γ and IL-2 production at both the mRNA and protein levels, and IL-12 expression at the mRNA level. In contrast, NSAIDs down-regulated IL-6 production both at the mRNA and protein levels, and down-regulated IL-4 mRNA expression. The modulation at the mRNA level became detectable 1 h after culture. This modulation was also observed at the level of TCC. Indomethacin (IM) enhanced TNF production in all the eight TCC that were established from a patient with human T lymphotrophic virus type 1 uveitis or pulmonary sarcoidosis, and suppressed IL-6 production in six of the eight TCC, without affecting their low levels of PGE2production. IM also enhanced TNF and suppressed IL-6 production, respectively, in both IL-2-activated PBMC and IL-2-dependent NK cell line, with the inhibition of their high levels of PGE2production. Culture with PGE2alone suppressed TNF production by three of the six TCC and NK cell lines, which was neutralized by addition of IM. It had, however, no effect on TNF production by the remaining three TCC or IL-2-activated PBMC. The effects of PGE2on IL-6 production also varied among TCC. These results suggest that NSAIDs up-regulate the mRNA expression and production of the cytokines (TNF, IFN-γ and IL-2) produced by T helper 1 cells, but down-regulate those of the cytokines (IL-4 and IL-6) produced by T helper 2 cells. This regulation may in part be independent of the inhibition of PGE2synthesis in TCC.

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