Systemic and local high mobility group box 1 concentrations during severe infection.
OBJECTIVE
High mobility group box 1 (HMGB1) has been implicated as a late mediator in sepsis. We here sought to determine the extent of HMGB1 release in patients with sepsis stratified to the three most common infectious sources and to determine HMGB1 concentrations at the site of infection during peritonitis or pneumonia.


METHODS
Observational studies in patients and healthy humans challenged with lipopolysaccharide.


METHODS
Three intensive care units and one clinical research unit.


METHODS
Three patient populations were studied: 1) 51 patients with sepsis due to pneumonia (n = 29), peritonitis (n = 12), or urinary tract infection (n = 10); 2) 17 patients with peritonitis; and 3) four patients with community-acquired pneumonia. In addition, eight healthy subjects were studied after intravenous injection of lipopolysaccharide (4 ng/kg).


METHODS
One population of healthy volunteers received lipopolysaccharide intravenously.


RESULTS
Patients with severe sepsis due to pneumonia displayed elevated circulating HMGB1 concentrations at both days 0 and 3 after inclusion. Patients with sepsis due to peritonitis had elevated HMGB1 levels at day 0 but not at day 3, whereas urinary tract infection was associated with a delayed HMGB1 response, with elevated levels only at day 3. HMGB1 concentrations did not differ between survivors and nonsurvivors and were not correlated to either disease severity or concurrently measured cytokine levels. In line with these observations, although intravenous lipopolysaccharide injection clearly elevated plasma cytokine levels, HMGB1 remained undetectable. In patients with peritonitis, HMGB1 concentrations in abdominal fluid were more than ten-fold higher than in concurrently obtained plasma. In pneumonia patients, HMGB1 levels were higher in bronchoalveolar lavage fluid obtained from the site of infection than in lavage fluid from healthy controls.


CONCLUSIONS
In severe sepsis, the kinetics of HMGB1 release may differ depending on the primary source of infection. In patients with severe infection, HMGB1 release may predominantly occur at the site of infection.
van Zoelen
Marieke A D
MA
Center for Infection and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. M.A.vanZoelen@amc.uva.nl
Laterre
Pierre-François
PF
van Veen
Suzanne Q
SQ
van Till
Jan W O
JW
Wittebole
Xavier
X
Bresser
Paul
P
Tanck
Michael W
MW
Dugernier
Thierry
T
Ishizaka
Akitoshi
A
Boermeester
Marja A
MA
van der Poll
Tom
T
D018806:APACHE; D000368:Aged; D016022:Case-Control Studies; D016207:Cytokines / Q000097:blood; D005260:Female; D024243:HMGB1 Protein / Q000378:metabolism*; D006801:Humans; D008070:Lipopolysaccharides; D008297:Male; D008875:Middle Aged; D010538:Peritonitis / Q000150:complications / Q000276:immunology*; D011014:Pneumonia / Q000150:complications / Q000276:immunology*; D018805:Sepsis / Q000209:etiology* / Q000276:immunology*; D016019:Survival Analysis; D014552:Urinary Tract Infections / Q000150:complications / Q000276:immunology*
D016207:Cytokines; D024243:HMGB1 Protein; D008070:Lipopolysaccharides