Inflammation is a natural, protective response of the body to harmful stimuli, such as infections, injuries and irritants. It involves a complex cascade of events involving various immune cells, chemical messengers and blood components. While inflammation plays a vital role in healing and tissue repair, it can also contribute to the development of chronic diseases when it becomes uncontrolled or persistent.
Pathophysiology
1. Initiating Events
- Cellular Damage: Injury, infection or exposure to irritants triggers inflammation by activating various receptors and signalling pathways on cells at the site of damage.
- PAMPs and DAMPs: Pathogen-associated molecular patterns (PAMPs) from invading microbes and damage-associated molecular patterns (DAMPs) released by injured cells act as danger signals, further activating the inflammatory response.
2. Vascular Changes
- Vasodilation: Mediated by histamine, prostaglandins and other inflammatory mediators, blood vessels in the affected area dilate, increasing blood flow and delivering immune cells and other inflammatory factors.
- Increased Vascular Permeability: Endothelial cells lining the blood vessels become activated, expressing adhesion molecules that attract white blood cells and allowing them to migrate into the inflamed tissue.
3. Immune Cell Recruitment and Activation
- Neutrophils: These are the first responders, quickly migrating to the site of inflammation to phagocytize bacteria and release antimicrobial factors.
- Monocytes and Macrophages: Monocytes differentiate into macrophages at the site of inflammation, phagocytising debris, presenting antigens to lymphocytes and releasing inflammatory mediators.
- Lymphocytes: B lymphocytes produce antibodies to neutralise pathogens, while T lymphocytes orchestrate the immune response and promote tissue repair.
4. Cytokine Cascade
- Activated immune cells and other tissue cells release a variety of cytokines, including TNF-α, IL-1, and IL-6.
- These cytokines have diverse effects, including:
- Amplifying the inflammatory response by attracting and activating immune cells.
- Promoting tissue repair by stimulating cell proliferation and differentiation.
- Inducing pain and fever.
5. Resolution and Repair
- Once the threat is neutralised, the inflammatory response subsides through active and passive mechanisms:
- Apoptotic neutrophils: Phagocytised debris and neutrophils undergo apoptosis, preventing the release of harmful substances.
- Anti-inflammatory mediators: Pro-resolving mediators, such as lipoxins and resolvins, actively dampen inflammation and promote tissue repair.
- Macrophage switch: Macrophages switch their phenotype from pro-inflammatory to pro-resolution, promoting wound healing and tissue regeneration.