@article{3163576,
    title = "The discriminative capacity of soluble Toll-like receptor (sTLR)2 and
sTLR4 in inflammatory diseases",
    author = "ten Oever, Jaap and Kox, Matthijs and De Veerdonk, Frank L. Van and and Mothapo, Khutso M. and Slavcovici, Adriana and Jansen, Tim L. and and Tweehuysen, Lieke and Giamarellos-Bourboulis, Evangelos J. and and Schneeberger, Peter M. and Wever, Peter C. and Stoffels, Monique and and Simon, Anna and Van der Meer, Jos Wm and Johnson, Melissa D. and and Kullberg, Bart-Jan and Pickkers, Peter and Pachot, Alexandre and Ab and Joosten, Leo and Netea, Mihai G.",
    journal = "BMC Immunology",
    year = "2014",
    volume = "15",
    publisher = "BMC",
    issn = "1471-2172",
    doi = "10.1186/s12865-014-0055-y",
    keywords = "Soluble Toll-like receptor; Biomarkers; Non-infectious inflammation;
Experimental human endotoxemia",
    abstract = "Background: The extracellular domains of cytokine receptors are released
during inflammation, but little is known about the shedding of Toll-like
receptors (TLR) and whether they can be used as diagnostic biomarkers.
Methods: The release of sTLR2 and sTLR4 was studied in in-vitro
stimulations, as well as in-vivo during experimental human endotoxemia
(n = 11, 2 ng/kg LPS), and in plasma of 394 patients with infections
(infectious mononucleosis, measles, respiratory tract infections,
bacterial sepsis and candidemia) or non-infectious inflammation (Crohn’s
disease, gout, rheumatoid arthritis, autoinflammatory syndromes and
pancreatitis). Using C-statistics, the value of sTLR2 and sTLR4 levels
for discrimination between infections and non-infectious inflammatory
diseases, as well as between viral and bacterial infections was
analyzed.
Results: In-vitro, peripheral blood mononuclear cells released sTLR2 and
sTLR4 by exposure to microbial ligands. During experimental human
endotoxemia, plasma concentrations peaked after 2 hours (sTLR4) and 4
hours (sTLR2). sTLR4 did not correlate with cytokines, but sTLR2
correlated positively with TNF alpha (r(s) = 0.80, P < 0.05), IL-6 (r(s)
= 0.65, P < 0.05), and IL-1Ra (r(s) = 0.57, P = 0.06), and negatively
with IL-10 (r(s) = -0.58, P = 0.06), respectively. sTLR4 had a similar
area under the ROC curve [AUC] for differentiating infectious and
non-infectious inflammation compared to CRP: 0.72 (95% CI 0.66-0.79)
versus 0.74 (95% CI 0.69-0.80) [P = 0.80], while sTLR2 had a lower
AUC: 0.60 (95% CI 0.54-0.66) [P = 0.0004]. CRP differentiated
bacterial infections better from viral infections than sTLR2 and sTLR4:
AUC 0.94 (95% CI 0.90-0.96) versus 0.58 (95% CI 0.51-0.64) and 0.75
(95% CI 0.70-0.80), respectively [P < 0.0001 for both].
Conclusions: sTLRs are released into the circulation, and suggest the
possibility to use sTLRs as diagnostic tool in inflammatory conditions."
}