- When tissues are damaged, cells in the affected area release a variety of molecules known as damage-associated molecular patterns (DAMPs).

These molecules can be intracellular components (like DNA, ATP, or proteins) that are released into the extracellular space.

- Pathogens or foreign substances can also trigger inflammation through pathogen-associated molecular patterns (PAMPs)

Activation of Immune Cells:
- DAMPs and PAMPs are recognized by pattern recognition receptors (PRRs) on the surface of immune cells, such as macrophages and dendritic cells.
- This recognition leads to the activation of these immune cells and the production of inflammatory mediators.

Release of Inflammatory Mediators:
- Activated immune cells release various inflammatory mediators, including cytokines (e.g., interleukins, tumor necrosis factor-alpha), chemokines, histamines, and prostaglandins.

 

Release of Prostaglandins

- These mediators increase blood flow to the injured area, causing redness and heat. They also increase the permeability of blood vessels, allowing immune cells, fluid, and proteins to move into the tissue, leading to swelling.

Recruitment of Immune Cells:
- Chemokines attract additional immune cells, such as neutrophils and monocytes, to the site of injury. These cells help to remove debris, pathogens, and dead cells.
- Neutrophils are among the first responders, arriving quickly to the site to perform phagocytosis (engulfing and digesting foreign particles and damaged cells).

Resolution and Healing:
- As the threat or damage is managed, the inflammatory response is regulated to prevent excessive tissue damage. Anti-inflammatory signals are produced to reduce inflammation and promote tissue repair.
- Macrophages play a critical role in this phase by switching from a pro-inflammatory to a tissue-repair phenotype, aiding in the resolution of inflammation and the promotion of tissue healing.

Restoration of Homeostasis:
- The goal of the inflammatory response is to eliminate the initial cause of cell injury, clear out necrotic cells and tissues, and establish a repair process that restores tissue function.
- Fibroblasts and other cells contribute to tissue repair by producing extracellular matrix components and promoting the formation of new blood vessels (angiogenesis).

The entire process is tightly regulated to ensure that inflammation is effective in dealing with injury or infection but does not cause excessive damage to the body's own tissues.

Minor host insults result in a localized inflammatory response that is transient and, in most cases, beneficial.

Major host insults follow a different trajectory.

A subset of these patients will die within 24 hours of hospital admission, succumbing to overwhelming tissue injury and immediate organ damage.

A second subgroup of patients who suffer a major host insult succumb to secondary organ damage remote from the injury site and die later (weeks) in their hospital course. They form an increasing percentage of the in hospital trauma-related deaths. A dysregulated, overwhelming systemic inflammatory response to the injury/hemorrhage and associated ischemia/reperfusion events has been implicated as the cause of multiple organ failure in these patients. Moreover, it has been linked to immune suppression that increases the risk of infectious complications and poor outcome.

Finally, a third subgroup, characterized by extended length of stay in the ICU, complicated postdischarge courses, and failure to regain/recover to their preinjury status, has been described and also linked to persistent inflammation and suppressed host protective immunity. The term persistent inflammation, immunosuppression, and catabolism syndrome (PICS) has been applied to this group.1 Recent data suggest that severely injured patients who are destined to die from their injuries, whether late in their hospital course or after discharge, differ from survivors only in the degree and duration of their dysregulated acute inflammatory response.1-3