Impaired monocyte IL-12 production before surgery as a predictive factor for the lethal outcome of postoperative sepsis.
OBJECTIVE
To investigate whether monocyte paralysis resistant to interferon-gamma (IFN-gamma) costimulation may exist before surgery and postoperative infection and may correlate with the outcome of postoperative sepsis.


BACKGROUND
Several studies have correlated monocyte paralysis during the course of sepsis with lethal outcome. Although the authors' previous work indicated that preoperative defects in monocyte interleukin (IL)-12 production are associated with the development of severe postoperative sepsis, the functional state of monocytes before surgery and infection and its significance for sepsis requires further analysis.


METHODS
In a prospective study, monocyte functions of 1,113 consecutive patients were examined before major visceral surgery. Monocytes were isolated from peripheral blood and were stimulated in vitro with IFN-gamma and lipopolysaccharide. The secretion of IL-12 p70, IL-12 p40, IL-10, and tumor necrosis factor was measured.


RESULTS
Preoperative monocyte secretion of IL-12 p70 and IL-12 p40 was significantly reduced in patients who developed lethal postoperative sepsis compared with sepsis survivors and patients with uneventful postoperative recovery. Moreover, preoperative monocyte IL-12 production was an independent predictive factor for the lethal outcome of postoperative sepsis by multivariate analysis. Preoperative monocyte IL-10 production was impaired in the sepsis group but did not correlate with death from sepsis. Preoperative monocyte tumor necrosis factor secretion was comparable between patients with uneventful recovery, sepsis survivors, and nonsurvivors. Thus, impaired preoperative monocyte IL-12 secretion in patients developing lethal postoperative sepsis did not result from an overproduction of IL-10 or from a generalized monocyte paralysis. The association between impaired preoperative monocyte IL-12 production and death from sepsis was also not explained by gender differences, underlying malignant disease, tumor type, neoadjuvant therapy, or age.


CONCLUSIONS
These results identify a selective preoperative defect in monocyte IL-12 production as a predictive factor for the lethal outcome of postoperative sepsis. These data suggest that a partial preoperative monocyte paralysis severely impairs the host defense against postoperative infection, resulting in an increased risk of lethal sepsis.
Weighardt
Heike
H
Department of Surgery, Klinikum rechts der Isar, Technische Universität München, Munich, Germany.
Heidecke
Claus-Dieter
CD
Westerholt
Alexandra
A
Emmanuilidis
Klaus
K
Maier
Stefan
S
Veit
Martin
M
Gerauer
Klaus
K
Matevossian
Edouard
E
Ulm
Kurt
K
Siewert
Jörg-Rüdiger
JR
Holzmann
Bernhard
B
D000276:Adjuvants, Immunologic / Q000378:metabolism*; D000368:Aged; D013505:Digestive System Surgical Procedures / Q000009:adverse effects; D017558:Elective Surgical Procedures / Q000009:adverse effects; D005260:Female; D006801:Humans; D018664:Interleukin-12 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism*; D017063:Outcome Assessment, Health Care; D011183:Postoperative Complications; D011237:Predictive Value of Tests; D011300:Preoperative Care; D011446:Prospective Studies; D018805:Sepsis / Q000209:etiology / Q000401:mortality* / Q000503:physiopathology*
D000276:Adjuvants, Immunologic; D018664:Interleukin-12