TY - JOUR
TI - The discriminative capacity of soluble Toll-like receptor (sTLR)2 and
sTLR4 in inflammatory diseases
AU - ten Oever, Jaap
AU - Kox, Matthijs
AU - De Veerdonk, Frank L. Van and
AU - Mothapo, Khutso M.
AU - Slavcovici, Adriana
AU - Jansen, Tim L. and
AU - Tweehuysen, Lieke
AU - Giamarellos-Bourboulis, Evangelos J. and
AU - Schneeberger, Peter M.
AU - Wever, Peter C.
AU - Stoffels, Monique and
AU - Simon, Anna
AU - Van der Meer, Jos Wm
AU - Johnson, Melissa D. and
AU - Kullberg, Bart-Jan
AU - Pickkers, Peter
AU - Pachot, Alexandre
AU - Ab
AU - Joosten, Leo
AU - Netea, Mihai G.
JO - BMC Immunology
PY - 2014
VL - 15
TODO - null
SP - null
PB - BMC
SN - 1471-2172
TODO - 10.1186/s12865-014-0055-y
TODO - Soluble Toll-like receptor; Biomarkers; Non-infectious inflammation;
Experimental human endotoxemia
TODO - 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.
ER -