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Organ-association phenomena during sepsis. TNF and IL-6 in different macrophages
Abstract:
Sepsis was induced in rats by cecal ligation and perforation (CLP). Five and 15 hours post CLP, alveolar macrophage (AM), Kupffer cell (KC), and peritoneal macrophage (PM) were isolated and cultured for 18 hours. Culture supernatant was examined for bioactivity of tumor necrosis factor (TNF) and interleukin 6 (IL-6) and response to lipoplysaccharide (LPS) stimulation in vitro. Results showed that AM produced more TNF during sepsis as compared with KC and PM. Stimulation with LPS in vitro was responded only by AM at 15 hr after CLP. Pattern of IL-6 production was different from TNF while KC produced the highest level of IL-6 after induction of sepsis.
Insights
Sepsis alters macrophage function. Alveolar macrophages (AMs) produced more tumor necrosis factor (TNF) during sepsis and responded to lipopolysaccharide (LPS) stimulation, unlike Kupffer cells (KCs) or peritoneal macrophages (PMs).
Area of Science:
- Immunology
- Cell Biology
- Sepsis Research
Background:
- Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection.
- Macrophages, including alveolar macrophages (AMs), Kupffer cells (KCs), and peritoneal macrophages (PMs), play critical roles in the immune response to sepsis.
- Understanding the differential responses of macrophage populations is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the differential production of inflammatory cytokines, tumor necrosis factor (TNF) and interleukin 6 (IL-6), by various macrophage populations during sepsis.
- To assess the in vitro responsiveness of these macrophages to lipopolysaccharide (LPS) stimulation following sepsis induction.
Main Methods:
- Sepsis was induced in rats using cecal ligation and perforation (CLP).
- Alveolar macrophages (AMs), Kupffer cells (KCs), and peritoneal macrophages (PMs) were isolated at 5 and 15 hours post-CLP.
- Macrophages were cultured, and their supernatants were analyzed for TNF and IL-6 bioactivity, and their response to in vitro LPS stimulation was evaluated.
Main Results:
- Alveolar macrophages (AMs) exhibited significantly higher TNF production during sepsis compared to Kupffer cells (KCs) and peritoneal macrophages (PMs).
- Only AMs isolated 15 hours post-CLP responded to in vitro lipopolysaccharide (LPS) stimulation.
- Interleukin 6 (IL-6) production patterns differed from TNF, with Kupffer cells (KCs) showing the highest IL-6 levels after sepsis induction.
Conclusions:
- Sepsis differentially impacts the cytokine production and inflammatory responsiveness of distinct macrophage populations.
- Alveolar macrophages (AMs) demonstrate a heightened pro-inflammatory state and retain responsiveness to LPS during sepsis.
- Kupffer cells (KCs) contribute significantly to IL-6 production during sepsis, suggesting specialized roles in the inflammatory cascade.