Inflammation

Inflammation is triggered is a number of ways:

• Macrophages recognise a pathogen and start to release cytokines.
• The complement system triggers degranulation of mast cells, basophils and eosinophils, releasing cytokines.
• Mast cells, basophils and eosinophils respond directly to allergens or tissue damage by degranulation, releasing cytokines.

Inflammation provides a positive feedback loop that activates these triggers further leading to greater inflammation.

Inflammation

Inflammation leads to a number of effects:

• Localised effects on local tissues
  • Activation of endothelial cells to display adhesion molecules
  • Vasodilation
  • Increased vascular permeability
• Activation of pro-inflammatory systems
  • Clotting system is activated
  • Kinin system is activated
  • Complement system is further activated
• Recruitment and activation of cells of the immune system
  • Further macrophages are activated
  • Monocytes are recruited to the site of inflammation and become macrophages
  • Mast cells and basophils are activated and release more cytokines
  • Eosinophils are activated and release more cytokines
  • Neutrophils are recruited to site of inflammation for phagocytosis
• Lead to an Acute Phase Response (neutrophils and macrophages respond to inflammation by releasing even more cytokines)
  • IL-1 act on the central nervous system to cause fever, lethargy and anorexia
  • IL-6 simulates the liver to produce acute phase proteins (opsonins)
  • IL-8 recruits and activates neutrophils
  • IL-2 and IL-12 activate natural killer cells
  • Tumour necrosis factor alpha (TNF-α) has the same action of all of the interleukins above

Recruitment of Cells

Inflammation causes more cells to be recruited to the site of an infection via:

• Localised vasodilation and increased vascular permeability allowing cells to easily leak from the blood to the site of infection
• Activation of localised adhesion molecules on endothelial cells of the blood vessels. These “catch” cells of the immune system and cause a localised influx of cells

Mast Cells and Basophils

Mast cells and basophils are activated by inflammation and release cytokines from their cytoplasmic granules (degranulation):

• Prostaglandins cause vasodilation and inhibit platelet aggregation (preventing clot formation)
• Leukotrienes cause contraction of airway smooth muscle, attraction of neutrophils to the area of inflammation and increased vascular permeability
• Heparin
• Histamine
• Enzymes

Acute Phase Proteins

Interleukin-6 stimulates the liver to release acute phase proteins. These molecules act as opsonins, helping phagocytes to eat and destroy pathogens. In clinical practice we measure CRP as a marker on inflammation, and it can be helpful in guiding our treatment of infections.

• C-reactive protein
• Fibrinogen
• Mannose-binding protein
• C3
• Haptoglobulin
• Serum Amyloid A

Clotting System

Increased production of fibrinogen by the liver and activation of the clotting cascade leads to clotting of blood. This helps to limit entry of pathogens into the blood stream.

Kinin System

Bradykinin causes contraction of airway smooth muscle, vasodilation, increased vascular permeability and pain.