Inducibility of the endogenous antibiotic peptide beta-defensin 2 is impaired in patients with severe sepsis.
BACKGROUND
The potent endogenous antimicrobial peptide human beta-defensin 2 (hBD2) is a crucial mediator of innate immunity. In addition to direct antimicrobial properties, different effects on immune cells have been described. In contrast to the well-documented epithelial beta-defensin actions in local infections, little is known about the leukocyte-released hBD2 in systemic infectious disorders. This study investigated the basic expression levels and the ex vivo inducibility of hBD2 mRNA in peripheral whole blood cells from patients with severe sepsis in comparison to non-septic critically ill patients and healthy individuals.


METHODS
This investigation was a prospective case-control study performed at a surgical intensive care unit at a university hospital. A total of 34 individuals were tested: 16 patients with severe sepsis, 9 critically ill but non-septic patients, and 9 healthy individuals. Serial blood samples were drawn from septic patients, and singular samples were obtained from critically ill non-septic patients and healthy controls. hBD2 mRNA levels in peripheral white blood cells were quantified by real-time polymerase chain reaction in native peripheral blood cells and following ex vivo endotoxin stimulation. Defensin plasma levels were quantified by enzyme-linked immunosorbent assay.


RESULTS
Endotoxin-inducible hBD2 mRNA expression was significantly decreased in patients with severe sepsis compared to healthy controls and non-septic critically ill patients (0.02 versus 0.95 versus 0.52, p < 0.05, arbitrary units). hBD2 plasma levels in septic patients were significantly higher compared to healthy controls and critically ill non-septic patients (541 versus 339 versus 295 pg/ml, p < 0.05).


CONCLUSIONS
In contrast to healthy individuals and critically ill non-septic patients, ex vivo inducibility of hBD2 in peripheral blood cells from septic patients is reduced. Impaired hBD2 inducibility may contribute to the complex immunological dysfunction in patients with severe sepsis.
Book
Malte
M
Department of Anaesthesiology and Intensive Care Medicine, Rheinische-Friedrich-Wilhelms University Bonn, Bonn, Germany. malte.book@ukb.uni-bonn.de
Chen
QiXing
Q
Lehmann
Lutz E
LE
Klaschik
Sven
S
Weber
Stefan
S
Schewe
Jens-Christian
JC
Luepertz
Markus
M
Hoeft
Andreas
A
Stuber
Frank
F
D000328:Adult; D016022:Case-Control Studies; D016638:Critical Illness; D015870:Gene Expression; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007962:Leukocytes / Q000378:metabolism; D011446:Prospective Studies; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood; D012016:Reference Values; D018805:Sepsis / Q000097:blood*; D023083:beta-Defensins / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics
C106641:DEFB4A protein, human; D015850:Interleukin-6; D012333:RNA, Messenger; D023083:beta-Defensins