Περίληψη:
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.
Συγγραφείς:
ten Oever, Jaap
Kox, Matthijs
De Veerdonk, Frank L. Van and
Mothapo, Khutso M.
Slavcovici, Adriana
Jansen, Tim L. and
Tweehuysen, Lieke
Giamarellos-Bourboulis, Evangelos J. and
Schneeberger, Peter M.
Wever, Peter C.
Stoffels, Monique and
Simon, Anna
Van der Meer, Jos Wm
Johnson, Melissa D. and
Kullberg, Bart-Jan
Pickkers, Peter
Pachot, Alexandre
Ab
Joosten, Leo
Netea, Mihai G.
