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Updated: Oct 9, 2026
Single-cell Analysis of Immunophenotype and Cytokine Production in Peripheral Whole Blood via Mass Cytometry
Published on: June 26, 2018
CD14 expression on monocytes and TNF alpha production in patients with septic shock, cardiogenic shock or bacterial
I de Werra1, G Zanetti, C Jaccard
1Department of Infectious Diseases, CHUV, Lausanne, Switzerland.
Objectives:
In patients with septic shock, circulating monocytes become refractory to stimulation with microbial products. Whether this hyporesponsive state is induced by infection or is related to shock is unknown. To address this question, we measured TNF alpha production by monocytes or by whole blood obtained from healthy volunteers (controls), from patients with septic shock, from patients with severe infection (bacterial pneumonia) without shock, and from patients with cardiogenic shock without infection.
Measurements:
The numbers of circulating monocytes, of CD14+ monocytes, and the expression of monocyte CD14 and the LPS receptor, were assessed by flow cytometry. Monocytes or whole blood were stimulated with lipopolysaccharide endotoxin (LPS), heat-killed Escherichia coli or Staphylococcus aureus, and TNF alpha production was measured by bioassay.
Results:
The number of circulating monocytes, of CD14+ monocytes, and the monocyte CD14 expression were significantly lower in patients with septic shock than in controls, in patients with bacterial pneumonia or in those with cardiogenic shock (p < 0.001). Monocytes or whole blood of patients with septic shock exhibited a profound deficiency of TNF alpha production in response to all stimuli (p < 0.05 compared to controls). Whole blood of patients with cardiogenic shock also exhibited this defect (p < 0.05 compared to controls), although to a lesser extent, despite normal monocyte counts and normal CD14 expression.
Conclusions:
Unlike patients with bacterial pneumonia, patients with septic or cardiogenic shock display profoundly defective TNF alpha production in response to a broad range of infectious stimuli. Thus, down-regulation of cytokine production appears to occur in patients with systemic, but not localised, albeit severe, infections and also in patients with non-infectious circulatory failure. Whilst depletion of monocytes and reduced monocyte CD14 expression are likely to be critical components of the hyporesponsiveness observed in patients with septic shock, other as yet unidentified factors are at work in this group and in patients with cardiogenic shock.
Insights
Patients with septic or cardiogenic shock show reduced TNF alpha production, unlike those with localized infections. This indicates systemic inflammation, not just infection, impairs immune response.
Area of Science:
- Immunology
- Critical Care Medicine
- Pathophysiology
Background:
- Septic shock leads to monocyte hyporesponsiveness to microbial stimuli.
- The cause of this hyporesponsiveness (infection vs. shock) is unclear.
Purpose of the Study:
- To investigate the cause of monocyte hyporesponsiveness in septic shock.
- To compare TNF alpha production in septic shock, non-shock severe infection, and cardiogenic shock.
Main Methods:
- Flow cytometry assessed monocyte counts and CD14 expression.
- Monocytes/whole blood stimulated with LPS and bacteria.
- TNF alpha production measured by bioassay.
Main Results:
- Septic shock patients had lower monocyte counts and CD14 expression.
- Septic shock and cardiogenic shock patients showed defective TNF alpha production.
- Cardiogenic shock patients had defects despite normal monocyte counts.
Conclusions:
- Systemic conditions (septic/cardiogenic shock) impair TNF alpha production.
- Localized infections (bacterial pneumonia) do not cause this defect.
- Monocyte depletion and CD14 downregulation contribute to septic shock hyporesponsiveness.
