Related Experiment Videos
[Cytokine storm in the pathogenesis of multiple organ dysfunction syndrome associated with surgical insults]
1Department of Emergency and Critical Care Medicine, School of Medicine, Keio University, Tokyo, Japan.
Abstract:
Multiple organ dysfunction syndrome (MODS) is a critical condition developing in the patients under overwhelming surgical insults such as a major surgery, severe trauma, extensive burn, and systemic sepsis. The host response to those surgical insults is the main pathogenetic factor contributing to the development of shock and MODS seen in surgical patients. The proinflammatory cytokines, TNF-alpha (TNF) and interleukin-1 beta (IL-1), are known to play a pivotal role in the pathogenetic mechanisms of MODS. In response to surgical insults, macrophages produce and release TNF and IL-1 which subsequently induce the production of other cytokines (IL-6, IL-8, etc.) and other endogenous chemical mediators (growth factors, adhesion molecules, complement cleavage products, thrombin, eicosanoids, PAF, nitric oxides, oxygen-free radicals, granulocyte elastase, etc.) The resultant systemic inflammation may develop into shock and MODS when the primary insults are overwhelming (early MODS) or a second inflammatory insult such as sepsis triggers an exaggerated inflammation. In the patients suffering from MODS, a systemic release of various cytokines is not properly regulated, and the high blood levels of the proinflammatory cytokines induce an autodestructive generalized inflammatory reaction. This condition is termed "Cytokine Storm" by the author. In the cytokine storm, not only proinflammatory cytokines but also anti-inflammatory cytokines are elevated in the blood stream. With the recent understanding of the biological and pathological roles of cytokines and other mediators, a new therapeutic strategy has been developed. In addition to the reduction of the surgical insults, a variety of anti-cytokine therapy and anti-mediator therapy has been tested in an attempt to prevent or treat the life-threatening MODS.
Insights
Surgical insults trigger a cytokine storm, leading to multiple organ dysfunction syndrome (MODS). New therapies target anti-cytokine and anti-mediator treatments to prevent and treat this critical condition.
Area of Science:
- Immunology
- Pathophysiology
- Critical Care Medicine
Context:
- Multiple organ dysfunction syndrome (MODS) is a critical condition following major surgery, trauma, burns, or sepsis.
- The host's inflammatory response to surgical insults is a key factor in developing shock and MODS.
- Pro-inflammatory cytokines like TNF-alpha and IL-1 beta play a central role in MODS pathogenesis.
Purpose:
- To elucidate the pathogenetic mechanisms of MODS, focusing on the role of cytokines and inflammatory mediators.
- To describe the "Cytokine Storm" phenomenon in MODS, characterized by dysregulated cytokine release.
- To introduce novel therapeutic strategies, including anti-cytokine and anti-mediator therapies for MODS.
Summary:
- Surgical insults provoke a host response involving macrophages producing TNF-alpha and IL-1 beta, initiating a cascade of inflammatory mediators.
- Overwhelming insults or secondary insults like sepsis can lead to an exaggerated inflammatory response, termed "Cytokine Storm," causing autodestructive inflammation.
- This storm involves both pro-inflammatory and anti-inflammatory cytokines, contributing to the systemic dysfunction seen in MODS.
Impact:
- Understanding the "Cytokine Storm" provides insights into the complex pathophysiology of MODS.
- Development of targeted anti-cytokine and anti-mediator therapies offers new avenues for preventing and treating life-threatening MODS.
- This research highlights the potential for immunomodulatory treatments in critical surgical and trauma patients.