Expression of monocyte human leukocyte antigen-DR in relation with sepsis severity and plasma mediators.
OBJECTIVE
After an initial septic hit, the immune response to a new antigen changes as time progresses, with an unpredictable efficiency. The aim of this study was to characterize the monocyte functional phenotype by HLA-DR expression in septic patients at the onset of sepsis and during recovery in relation to organ failure and plasma mediators.


METHODS
Twenty-six patients were analyzed as either single organ failure at worst (SOF) or multiple organ failure (MOF) over 14 days. Twelve patients received immunosuppressive (IS) drugs before sepsis. We measured: 1) monocyte HLA-DR expression (mHLA-DR); 2) plasma pro-inflammatory mediators (IL-12p40, macrophage Migration Inhibitory Factor [MIF]); 3) plasma anti-inflammatory mediators (IL-10, cortisol); and 4) in vitro lipopolysaccharide (LPS) stimulated mHLA-DR in 6-hour whole blood culture or after plasma replacement with standard milieu.


RESULTS
mHLA-DR expression was equally decreased in patients who were treated with IS drugs as those who were not. Despite the difference in severity, SOF patients showed a similar profound mHLA-DR downregulation as MOF patients at day 0, but tended to recover earlier. MOF patients presented higher plasma IL-10 and cortisol levels than SOF patients but similar plasma IL-12p40 and MIF levels. In vitro LPS stimulation showed an impaired mHLA-DR response in both groups. Plasma replacement by milieu elicited a slight improvement in the response to LPS in SOF but not MOF patients.


CONCLUSIONS
At the onset of sepsis, an initial low mHLA-DR was not related to any prior IS drug regimen, the severity of the sepsis or the outcome. The duration of mHLA-DR downregulation could be related to plasma factors in SOF, while other mechanisms may be implicated in MOF evolution.
Payen
D
D
Department of Anesthesiology, Royal Victoria Hospital, McGill University, Montréal, QC, Canada dpayen1234@aol.com
Faivre
V
V
Lukaszewicz
A C
AC
Villa
F
F
Goldberg
P
P
D000328:Adult; D000368:Aged; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006684:HLA-DR Antigens / Q000096:biosynthesis*; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018836:Inflammation Mediators / Q000378:metabolism*; D007958:Leukocyte Count; D008070:Lipopolysaccharides; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D018805:Sepsis / Q000378:metabolism*; D055815:Young Adult
D016207:Cytokines; D006684:HLA-DR Antigens; D007166:Immunosuppressive Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D006854:Hydrocortisone