The central role of monocytes in the pathogenesis of sepsis: consequences for immunomonitoring and treatment.
Despite important advances in critical care medicine during the last two decades, the mortality rate of sepsis has remained high, probably because the pathogenesis of sepsis is still incompletely understood. Recent studies have shown that sepsis is a bimodal entity. The first phase is characterized by the systemic release of pro-inflammatory cytokines such as tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1), and IL-8, and by activation of the complement and coagulation cascades. In the second phase, anti-inflammatory mediators such as transforming growth factor-beta (TGF-beta), IL-10 and prostaglandin E2 (PGE2) may be released in an effort to counteract ongoing inflammation. Depending whether the pro- or anti-inflammatory response predominates, sepsis results in a systemic inflammatory response syndrome (SIRS), or a compensatory anti-inflammatory response syndrome (CARS). So far, most efforts to intervene in the immunopathogenesis of sepsis have been directed at the pro-inflammatory response. None of these interventions has been shown to improve the prognosis of sepsis, possibly because many patients were already in a state in which anti-inflammatory responses dominated. Recently, it has been shown that decreased expression of HLA-DR on monocytes in patients with sepsis constitutes a marker for CARS. We suggest that HLA-DR expression on monocytes might constitute a useful indicator of the immunological status of the individual patient with sepsis and a guide for treatment. Patients with CARS, as manifested by low HLA-DR expression, might benefit from immunostimulants, while patients with SIRS and normal or high monocyte HLA-DR expression should receive treatment directed to interfere with pro-inflammatory pathways.
Haveman
J W
JW
Department of Clinical Immunology, University Hospital Groningen, The Netherlands.
Muller Kobold
A C
AC
Tervaert
J W
JW
van den Berg
A P
AP
Tulleken
J E
JE
Kallenberg
C G
CG
The
T H
TH
D015415:Biomarkers; D006684:HLA-DR Antigens / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007116:Immunization, Passive; D008954:Models, Biological; D015166:Monitoring, Immunologic; D009000:Monocytes / Q000276:immunology / Q000378:metabolism*; D018805:Sepsis / Q000276:immunology* / Q000628:therapy
D015415:Biomarkers; D006684:HLA-DR Antigens