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Updated: Aug 17, 2026
Design of Cecal Ligation and Puncture and Intranasal Infection Dual Model of Sepsis-Induced Immunosuppression
Published on: June 15, 2019
Selective macrophage suppression during sepsis
Ekram Ellaban1, Gerry Bolgos, Daniel Remick
1Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
Abstract:
Polymicrobial sepsis induces suppression of macrophage function as determined by a reduction of pro-inflammatory cytokine production upon re-exposure to lipopolysaccharide (LPS) in vitro. We examined whether macrophages were refractory to only LPS challenge or if they were immunoparalyzed and unable to respond to other stimuli such as lipoteichoic acid (LTA) or zymosan (ZYM). This study evaluated the capacity of peritoneal macrophages to produce pro-inflammatory and anti-inflammatory cytokines as well as chemokines following mild or severe sepsis induced by cecal ligation and puncture (CLP). Peritoneal macrophages were isolated 29 h after CLP and challenged with different stimuli. LPS was a more potent stimulus for cytokine induction than LTA or ZYM in both mild and severe sepsis. In mild sepsis, the macrophage cytokine response to LPS was selective and less refractory than in severe sepsis. While production of IL-6 and KC was reduced, secretion of TNF-alpha and MIP-1alpha was enhanced in those cells isolated from mice with mild sepsis. Production of IL-10 and the IL-1 receptor antagonist , MIP-2, and MCP-1 in response to LPS stimulation was equivalent to the amount produced by naive macrophages. Our results indicate that macrophages are not immunoparalyzed during sepsis and may still be induced to secrete some inflammatory mediators.
Insights
Sepsis impairs macrophage function, but they are not completely paralyzed. Macrophages can still produce inflammatory mediators, especially in milder sepsis cases, indicating a selective rather than a complete loss of immune response.
Area of Science:
- Immunology
- Microbiology
- Pathophysiology
Background:
- Polymicrobial sepsis is known to suppress macrophage function.
- Reduced pro-inflammatory cytokine production after lipopolysaccharide (LPS) re-exposure suggests impaired macrophage activity.
- It remains unclear if macrophages are broadly immunoparalyzed or only refractory to specific stimuli like LPS.
Purpose of the Study:
- To investigate the functional status of peritoneal macrophages during sepsis.
- To determine if macrophages are broadly unresponsive (immunoparalyzed) or selectively impaired in their response to various immune stimuli.
- To evaluate cytokine and chemokine production by macrophages following mild or severe sepsis induced by cecal ligation and puncture (CLP).
Main Methods:
- Cecal ligation and puncture (CLP) was used to induce mild and severe polymicrobial sepsis in mice.
- Peritoneal macrophages were isolated 29 hours post-CLP.
- Isolated macrophages were stimulated in vitro with lipopolysaccharide (LPS), lipoteichoic acid (LTA), or zymosan (ZYM) to assess cytokine and chemokine production.
Main Results:
- Lipopolysaccharide (LPS) was a more potent stimulus for cytokine induction than lipoteichoic acid (LTA) or zymosan (ZYM) in both mild and severe sepsis.
- In mild sepsis, macrophage responses to LPS were selective and less impaired compared to severe sepsis.
- While IL-6 and KC production decreased, TNF-alpha and MIP-1alpha secretion increased in macrophages from mildly septic mice; IL-10, IL-1 receptor antagonist, MIP-2, and MCP-1 levels were comparable to naive macrophages.
Conclusions:
- Macrophages are not completely immunoparalyzed during sepsis.
- The immune response of macrophages during sepsis is stimulus-dependent and can be selective.
- Macrophages retain the capacity to secrete inflammatory mediators even during sepsis, particularly in less severe forms.