Reprogramming of circulatory cells in sepsis and SIRS

Area of Science:

• Immunology
• Critical Care Medicine

Background:

• Sepsis and systemic inflammatory response syndrome (SIRS) significantly alter immune status.
• Reduced ex-vivo tumor necrosis factor (TNF) production by endotoxin-activated monocytes is a commonly reported finding.
• This hyporesponsiveness is often termed 'leukocyte reprogramming', similar to endotoxin tolerance.

Purpose of the Study:

• To review the phenomenon of leukocyte reprogramming in sepsis and SIRS.
• To challenge the notion of generalized hyporesponsiveness of circulating leukocytes.
• To highlight factors influencing immune cell responses in these conditions.

Main Methods:

• Review of existing literature on immune cell function in sepsis and SIRS.
• Analysis of studies investigating ex-vivo immune cell activation and cytokine production.
• Comparison of responses based on different experimental conditions and patient insults.

Main Results:

• Leukocyte hyporesponsiveness in sepsis and SIRS is not a generalized phenomenon.
• The observed immune response is highly dependent on the nature of the inflammatory insult (infectious vs. non-infectious SIRS, surgical vs. non-surgical).
• Variations in leukocyte activators, cell culture methods, and analyzed cytokines profoundly influence experimental outcomes.

Conclusions:

• The concept of 'leukocyte reprogramming' requires nuanced interpretation in the context of sepsis and SIRS.
• Immune cell behavior is context-dependent, influenced by multiple interacting factors.
• Further research is needed to fully elucidate the complexities of immune modulation in critical illness.