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Deree, J., Martins, J.O., Melbostad, H., Loomis, W.H. and Coimbra, R. (2008) Insights into the Regulation of TNF-α Production in Human Mononuclear Cells: The Effects of Non-Specific Phosphodiesterase Inhibition. Clinics, 63, 321- 328.

has been cited by the following article:

  • TITLE: Is There a Relation between Adenosine and Caffeines’ Mechanisms of Action and Toll-Like Receptor-4 (TLR-4)?

    AUTHORS: Sarah Moodad, Nayla Al-Akl, Joseph Simaan, Alexander M. Abdelnoor

    KEYWORDS: TLR-4, Adenosine, Caffeine, LPS-RS, Cytokines

    JOURNAL NAME: Open Journal of Immunology, Vol.5 No.4, September 4, 2015

    ABSTRACT: Previous studies showed that endogenous adenosine, an anti-inflammatory agent, was released at sites of injury and inflammation thereby decreasing the excessive production of pro-inflammatory cytokines. Caffeine, a non-specific adenosine blocker, has been reported in several studies to have opposing immune-modulatory effects. In this study, the effects of caffeine and adenosine on TLR-4 in promoting or decreasing the production of TNF-α and IL-12 by LPS-stimulated monocytes were investigated. Monocytes were isolated using Pluribead® kit from pooled blood obtained from ten volunteers. The monocytes were then incubated for 24 hours with Lipopolysaccharide (pLPS) extracted from Escherichia coli (aTLR-4 ligand activator), adenosine, caffeine and LPS extracted from Rhodobacter sphaeroides (LPS-RS, a TLR-4 ligand blocker), each alone or in different combinations. Later, the levels of pro-inflammatory cytokines TNFα and IL-12 were assessed in supernatants using an Enzyme Linked Immuno Assay (ELISA). Caffeine and adenosine significantly reduced the amount of TNFα and IL-12 produced by LPS-stimulated monocytes. Regarding non-stimulated and LPS-RS blocked monocytes, the presence of adenosine and caffeine significantly decreased TNFα levels produced by these cells but had little or non-significant effect on the levels of IL-12. In conclusion, both caffeine and adenosine blocked the production of the pro-inflammatory cytokines by pLPS-stimulated-monocytes. TLR-4 did not appear to be involved in the signaling pathway of caffeine and adenosine since blocking of TLR-4 did not abolish the effects of adenosine and caffeine on production of cytokines, in particular TNF-α.