Chronic inflammation is one of the possible outcomes of acute inflammation.

 

Causes of chronic inflammation

Chronic inflammation can occur due to:

• Persistent infections (e.g. tubercle bacillus)
• Persistent toxic agents (silica)
• Auto-immunity

Cells of chronic inflammation

Numerous inflammatory cells can be involved in chronic inflammation. These include:

• Macrophages
• Endothelial cells
• Fibroblasts
• Lymphocytes
• Eosinophils

Tissue macrophages are derived from the bone marrow in an immature form – monocyte.

They are slower to accumulate at sites of inflammation.

They are:

• Effector cell with a phagocytic role
• Mediator cells, the “conductor of the inflammatory orchestra”

Activation of macrophages

Macrophages are activated by other components of the inflammatory milieu:

• Endotoxin
• Interferon-γ from T cells
• Natural Killer (NK) cells

After activation, macrophages increase their:

• Size
• Metabolism
• Levels of lysosomal enzymes
• Phagocytic activity
• Ability to kill phagocytosed micro-organisms

However, they can also cause bystander tissue damage.

Macrophages as effector cells

Macrophages are capable of exerting their own direct influence by acting as effector cells. They can:

• Phagocytose and kill micro-organisms
• Phagocytose cell debris
• Phagocytose foreign material

This prepares the local environment for granulation tissue formation (angiogenesis and extracellular matrix deposition).

Macrophages as mediators

Activated macrophages produce a panoply of soluble mediators including:

• Platelet-derived growth factor
• Fibroblast growth factor
• Transforming growth factor β

All of these stimulate fibroblasts in different ways. PDGF can promote angiogenesis. This combination leads to granulation tissue formation.

Lymphocytes in chronic inflammation

• Add specificity to macrophage response
• Give rise to plasma cells secreting antibodies
• Can be cytotoxic

Eosinophils (EΦ) in chronic inflammation

• Attracted by substances released by macrophages
• Major basic protein kills helminthic parasites (schistosomiasis etc.)

Plasma cells in chronic inflammation

Plasma cells that produce antibody. They are generated from B lymphocytes. They have:

• Nucleus at one end of the cell (a)
• Chromatin in coarse blobs beneath the nuclear membrane (b)
• Basophilic cytoplasm (c)

 

Granulomas form by the accumulation of macrophages with ‘harder, denser’ cytoplasm (epithelioid cells) and multinucleated giant cells. They are associated with TB, sarcoidosis, leprosy etc.. They can be seen with foreign bodies and in autoimmune disease. Caseous necrosis can be found in the centre of large granulomas in mycobacterial infection.

Systemic inflammatory mediators induce a range of systemic effects:

• Fever
• Acute phase reaction proteins production (CRP, fibrinogen, serum amyloid A)
• Metabolic changes, the breakdown of muscle protein, changes in glucose metabolism – prepares for starvation

These changes modify the environment in which inflammatory response takes place. Macrophage-derived IL-1 is a critical mediator.

Inflammation is an adaptive response that:

• Removes injurious stimulus
• Initiates healing
• Is usually beneficial