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Inflammation resolution circuits are uncoupled in acute sepsis and correlate with clinical severity
- Source :
- JCI Insight
- Publication Year :
- 2021
- Publisher :
- American Society for Clinical Investigation, 2021.
-
Abstract
- Sepsis is a critical illness characterized by dysregulated inflammatory responses lacking counter-regulation. Specialized proresolving mediators are agonists for antiinflammation and for promoting resolution, and they are protective in preclinical sepsis models. Here, in human sepsis, we mapped resolution circuits for the specialized proresolving mediators resolvin D1 and resolvin D2 in peripheral blood neutrophils and monocytes, their regulation of leukocyte activation and function ex vivo, and their relationships to measures of clinical severity. Neutrophils and monocytes were isolated from healthy subjects and patients with sepsis by inertial microfluidics and resolvin D1 and resolvin D2 receptor expression determined by flow cytometry. The impact of these resolvins on leukocyte activation was determined by isodielectric separation and leukocyte function by stimulated phagolysosome formation. Leukocyte proresolving receptor expression was significantly higher in sepsis. In nanomolar concentrations, resolvin D1 and resolvin D2 partially reversed sepsis-induced changes in leukocyte activation and function. Principal component analyses of leukocyte resolvin receptor expression and responses differentiated sepsis from health and were associated with measures of sepsis severity. These findings indicate that resolvin D1 and resolvin D2 signaling for antiinflammation and resolution are uncoupled from leukocyte activation in early sepsis and suggest that indicators of diminished resolution signaling correlate with clinical disease severity.
- Subjects :
- Male
Pulmonology
Docosahexaenoic Acids
Neutrophils
Receptor expression
Inflammation
Immunologic Tests
In Vitro Techniques
Monocytes
Neutrophil Activation
Flow cytometry
Sepsis
chemistry.chemical_compound
Inflammation resolution
Bacterial infections
Humans
Medicine
Clinical severity
Immunity, Cellular
Principal Component Analysis
medicine.diagnostic_test
business.industry
Cellular immune response
General Medicine
Middle Aged
medicine.disease
chemistry
Immunology
Female
Inflammation Mediators
medicine.symptom
business
Resolvin
Ex vivo
Research Article
Signal Transduction
Subjects
Details
- ISSN :
- 23793708
- Database :
- OpenAIRE
- Journal :
- JCI Insight
- Accession number :
- edsair.doi.dedup.....6b86f127a6d3ffbd756722d7f44af9e2