Part of the TeachMe Series

Chronic Inflammation

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Original Author(s): Jess Speller
Last updated: 27th January 2021
Revisions: 8

Original Author(s): Jess Speller
Last updated: 27th January 2021
Revisions: 8

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Inflammation is the tissue’s response to injury. It describes a series of processes initiated to limit damage to tissue. Chronic inflammation also arises as a response to injury but takes place over a longer period of time than acute inflammation. The process is less stereotyped than acute inflammation and has an overlap with host immunity.

This article discusses how chronic inflammation arises, the cell types involved and clinical examples.

How Can It Arise?

Chronic inflammation is a combination of inflammation, tissue injury and repair.

There are a number of situations in which chronic inflammation may arise:

  • Chronic inflammation may ‘take over’ from acute inflammation if the damage does not resolve or the immune system fails to eradicate the causative agent.
  • It may arise de novo, e.g. in autoimmune conditions such as rheumatoid arthritis. This leads to excessive or inappropriate immune system activation.
  • It may develop alongside acute inflammation in severe and persistent irritation. This can happen due to recurrent episodes of acute inflammation.

Hallmarks of chronic inflammation

  • Infiltration with mononuclear cells –  Macrophages, lymphocytes and monocyte replace neutrophils. These cells have longer life-spans than neutrophils and so persist in the tissue.
  • Tissue destruction- This can be a result of prolonged exposure to pathogens, toxins or immune cell activation.
  • Healing – Damaged tissue attempts to heal through fibrosis and angiogenesis.

Cells Involved

The microscopic appearance of chronic inflammation is more varied than that of acute inflammation. It is generally described in terms of the cells that are present:

  • Macrophages are present in acute and chronic inflammation. They are important for phagocytosis, antigen presentation and cytokine synthesis.
  • Lymphocytes have many immunological functions. For instance, B cells differentiate to produce antibodies and T-cells have cytotoxic functions. T-cells can also produce interferon-ϒ which recruits monocytes and activates macrophages.
  • Plasma cells are differentiated antibody-producing B lymphocytes. Their presence indicates that inflammation has been present for a considerable amount of time.
  • Eosinophils are often found in allergic reactions and parasitic infections. Eotaxin recruits eosinophils which have granules containing major basic protein. This is toxic to parasites and host epithelial cells.
  • Fibroblasts/Myofibroblasts are recruited by macrophages. They produce collagen to assist in healing and repair.

The morphology of chronic inflammation is fairly non-specific. However, the proportions of each cell type will vary depending on the condition. For example, Plasma cells are prevalent in rheumatoid arthritis, whereas in chronic gastritis, lymphocytes are typically more abundant.

Fig 1 – Microscopy showing normal prostate tissue on the left and prostate tissue with a chronic inflammatory infiltrate on the right.

Giant Cells

Giant cells are multi-nucleated cells, made by the fusion of multiple macrophages. They form as a result of frustrated phagocytosis, which is when a phagocyte fails to engulf its target. There are several types, with some recognised in different conditions:

  • Langhans Giant Cell in tuberculosis.
  • Foreign-body Type Giant Cell.
  • Touton Giant Cell in fat necrosis.

Fig 2 – Microscopy showing a Langhans Giant Cell centrally

Granulomas

Granulomas are a collection of epithelioid histiocytes (macrophages) that may form in chronic inflammation. They may also have associated lymphocytes or an area of central necrosis.

They arise as a result of persistent, low-grade antigenic stimulation or hypersensitivity. The immune system is unable to eliminate the substance and, subsequently, attempts to ‘wall it off’ from the surrounding tissues. Some examples of diseases which feature granulomatous inflammation include: tuberculosis, leprosy and Crohn’s disease.

Fig 3 – Microscopy showing a granuloma found in a lymph node biopsy. Cultures grew Mycobacterium avium.

Effects of Chronic Inflammation

Chronic inflammation can have several complications depending on the area and underlying disease process. These include:

  • Fibrosis, e.g. chronic cholecystitis can lead to fibrosis of the gall bladder wall.
  • Impaired function, e.g. inflammatory bowel disease.
  • Atrophy, e.g. atrophy of gastric mucosa in gastritis.
  • Stimulation of immune response, e.g. local and systemic immune effects of rheumatoid arthritis.

Clinical Relevance – Pulmonary Tuberculosis

Tuberculosis (TB) is an infection typically caused by mycobacterium tuberculosis. It normally affects the lungs. However, TB can infect other areas of the body. Most cases are asymptomatic, so-called latent TB. Nevertheless, around 10% of latent infections will progress to active disease. Common symptoms of active pulmonary TB include:

  • Chronic cough
  • Haemoptysis
  • Fever
  • Night sweats
  • Weight loss

Diagnosis of active TB is based on chest X-ray and Ziehl-Neelsen staining of sputum (as mycobacteria do not grow on other stains). Tuberculin skin test identifies latent TB.

Treatment is complex and long-term. Patients take a combination of Rifampicin, Isoniazid, pyrazinamide and ethambutol for the first 2 months then continue on rifampicin and isoniazid for the following 4 months.

Hint: use the mnemonic ‘RIPE’ to remember the above drug combination.

Fig 4 – Chest X-Ray of a patient with pulmonary TB. The white arrows indicate pulmonary infiltrate, while the black arrows indicate cavitation