Cotinine inhibits the pro-inflammatory response initiated by multiple cell surface Toll-like receptors in monocytic THP cells
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Microbiology and Immunology, University of Louisville, Louisville, USA
Currently: Department of Pediatrics, Washington University School of Medicine, St. Louis, USA
Oral Health and Systemic Disease Research Group, University of Louisville, Louisville, USA
Submission date: 2012-10-18
Acceptance date: 2012-11-21
Publication date: 2012-11-23
Corresponding author
David A Scott   

Microbiology and Immunology, University of Louisville, Louisville, KY 40292, USA
Tobacco Induced Diseases 2012;10(November):18
The primary, stable metabolite of nicotine [(S)-3-(1-methyl-2-pyrrolidinyl) pyridine] in humans is cotinine [(S)-1-methyl-5-(3-pyridinyl)-2-pyrrolidinone]. We have previously shown that cotinine exposure induces convergence and amplification of the GSK3β-dependent PI3 kinase and cholinergic anti-inflammatory systems. The consequence is reduced pro-inflammatory cytokine secretion by human monocytes responding to bacteria or LPS, a TLR4 agonist.

Here we show that cotinine-induced inflammatory suppression may not be restricted to individual Toll-like receptors (TLRs). Indeed, in monocytic cells, cotinine suppresses the cytokine production that is normally resultant upon agonist-specific engagement of all of the major surface exposed TLRs (TLR 2/1; 2/6; 4 and 5), although the degree of suppression varies by TLR.

These results provide further mechanistic insight into the increased susceptibility to multiple bacterial infections known to occur in smokers. They also establish THP-1 cells as a potentially suitable model with which to study the influence of tobacco components and metabolites on TLR-initiated inflammatory events.

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