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Expression of monocyte human leukocyte antigen-DR in relation with sepsis severity and plasma mediators
D Payen1, V Faivre, A C Lukaszewicz
1Department of Anesthesiology, Royal Victoria Hospital, McGill University, Montréal, QC, Canada dpayen1234@aol.com
Aim:
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.
Insights
Sepsis initially lowers monocyte HLA-DR expression regardless of severity or prior immunosuppressive drugs. Recovery varies, with plasma factors potentially influencing duration in single organ failure but not multiple organ failure.
Area of Science:
- Immunology
- Critical Care Medicine
- Pathophysiology
Background:
- Sepsis alters immune responses, impacting monocyte function unpredictably.
- Monocyte human leukocyte antigen-DR (mHLA-DR) expression reflects immune cell activation and is crucial for antigen presentation.
Purpose of the Study:
- To characterize monocyte functional phenotype via mHLA-DR in sepsis patients.
- To correlate mHLA-DR expression with organ failure severity and plasma mediators during sepsis onset and recovery.
Main Methods:
- Assessed mHLA-DR expression in 26 septic patients (single vs. multiple organ failure) over 14 days.
- Measured plasma cytokines (IL-12p40, MIF, IL-10) and cortisol.
- Evaluated in vitro LPS-stimulated mHLA-DR response and effect of plasma replacement.
Main Results:
- Initial mHLA-DR was profoundly downregulated in both single and multiple organ failure patients, irrespective of prior immunosuppressive drug use.
- Multiple organ failure patients had higher IL-10 and cortisol levels.
- In vitro stimulation showed impaired mHLA-DR response, with limited improvement upon plasma replacement in multiple organ failure.
Conclusions:
- Early sepsis-induced mHLA-DR downregulation is not linked to drug regimen, sepsis severity, or outcome.
- Plasma factors may influence mHLA-DR recovery duration in single organ failure, unlike multiple organ failure where other mechanisms are likely involved.
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