Author(s)

Sarah Moodad¹, Nayla Al-Akl¹, Joseph Simaan², Alexander M. Abdelnoor^1*

¹Department of Experimental Pathology, Immunology and Microbiology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
²Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.

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.

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

Moodad, S. , Al-Akl, N. , Simaan, J. and Abdelnoor, A. (2015) Is There a Relation between Adenosine and Caffeines’ Mechanisms of Action and Toll-Like Receptor-4 (TLR-4)?. Open Journal of Immunology, 5, 215-221. doi: 10.4236/oji.2015.54017.