Coincidence of pro- and anti-inflammatory responses in the early phase of severe sepsis: Longitudinal study of mononuclear histocompatibility leukocyte antigen-DR expression, procalcitonin, C-reactive protein, and changes in T-cell subsets in septic and postoperative patients.
OBJECTIVE
To determine the time course of histocompatibility leukocyte antigen (HLA)-DR expression in peripheral blood mononuclear cells and their relationship to markers of inflammation, organ function, and outcome during severe sepsis.


METHODS
Prospective, longitudinal study.


METHODS
University hospital intensive care unit.


METHODS
Twenty-three postoperative patients with severe sepsis and 26 patients with uneventful postoperative course as well as 24 healthy, age-matched subjects.


METHODS
Serum procalcitonin was determined by using an immunochemiluminescence assay, and C-reactive protein and leukocyte antigens were determined by using flow cytometry over 14 days in parallel with clinical data collection.


RESULTS
Despite a relative lymphopenia, absolute lymphocyte counts and CD4+/CD8+ T-cell ratio in septic patients were significantly elevated above normal. Particularly, CD4+ and CD8+ T-cell counts in nonsurvivors of sepsis were approximately twice as high as those of survivors. Significantly decreased monocytic HLA-DR expression was observed in both survivors and nonsurvivors at the onset of severe sepsis. Percentages of HLA-DR+ lymphocytes, however, were significantly increased during sepsis, especially in nonsurvivors. Whereas survivors of sepsis showed a continuous recovery of monocytic HLA-DR expression to >or=70% within 10 days, nonsurvivors were characterized by a second decrease in monocytic HLA-DR expression after day 7 or a permanent suppression (<40%). Peak of systemic inflammatory reaction, documented by maximum serum concentrations of procalcitonin and C-reactive protein, coincided with the nadir of monocytic HLA-DR expression. Moreover, procalcitonin and C-reactive protein as well as scores on the Acute Physiology and Chronic Health Evaluation II and Sepsis Organ Failure Assessment were inversely correlated with the monocytic HLA-DR expression.


CONCLUSIONS
Decreases in monocytic HLA-DR expression occurred simultaneously with signs of hyperinflammation as early as the onset of severe sepsis and usually developed in opposite directions than inflammatory markers and sepsis severity scores.
Tschaikowsky
Klaus
K
Department of Anesthesiology, University of Erlangen-Nürnberg, Erlangen, Germany.
Hedwig-Geissing
Monika
M
Schiele
Albert
A
Bremer
Frank
F
Schywalsky
Michael
M
Schüttler
Jürgen
J
D000368:Aged; D002097:C-Reactive Protein / Q000032:analysis*; D002116:Calcitonin / Q000097:blood*; D015740:Calcitonin Gene-Related Peptide; D005260:Female; D005434:Flow Cytometry; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D007249:Inflammation / Q000097:blood* / Q000276:immunology*; D008137:Longitudinal Studies; D008297:Male; D009000:Monocytes / Q000276:immunology*; D011184:Postoperative Period; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood*; D018805:Sepsis / Q000097:blood* / Q000276:immunology*; D016176:T-Lymphocyte Subsets
C000606589:CALCA protein, human; D006684:HLA-DR Antigens; D011498:Protein Precursors; D002116:Calcitonin; D002097:C-Reactive Protein; D015740:Calcitonin Gene-Related Peptide