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Original Author(s): Will Woodward
Last updated: 23rd January 2021
Revisions: 6

Original Author(s): Will Woodward
Last updated: 23rd January 2021
Revisions: 6

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Cytokines (literally “cell movement”) are a group of small proteins used in cell signalling. They are produced by a wide range of cells, including macrophages, lymphocytes, mast cells, endothelial cells and fibroblasts. They are responsible for producing some of the cardinal signs of inflammation and influence both the innate and adaptive immune responses. There are many types of cytokines which have been placed into different classes including chemokines, interferons, interleukins, lymphokines and tumour necrosis factors.

In this article we will look at different classes of cytokines and their actions.

Chemokines

Chemokines induce chemotaxis (chemical-induced migration) in local cells. Following the release of chemokines, local cells are attracted to these proteins and follow their concentration gradient to the source, where the concentration is highest. The source is where the chemokines were originally released and where the cells attracted are most needed. They are mainly produced by macrophages during infection, for example IL-8, which subsequently recruits neutrophils to the site during the acute phase response.

Chemokines can have many actions within tissues. These can be:

  • Pro-inflammatory actions- recruiting immune cells to the site of infection or trauma.
  • Homeostatic actions – for instance, attracting cells required for angiogenesis and allowing for the growth of new blood vessels.

Fig 1 – Diagram demonstrating the process of chemotaxis. The cell moves along the concentration gradient of chemokine to reach the area of highest concentration.

Interferons

Interferons are released by host cells in response to pathogens (e.g. viruses and bacteria) and tumour cells.

These cytokines have a number of roles, including:

  • Interfering (hence their name) with viral replication which helps the immune system fight viral infections – for example, through interferon-α and interferon-β.
  • Activating macrophages – for example, through interferon-γ.
  • Increase MHC expression.

Interleukins

Interleukins are produced by T lymphocytes, monocytes and macrophages. They have a wide range of functions, including:

  • Promoting the production and differentiation of B and T lymphocytes – Specifically, IL-1α/β, IL-4, IL-7 and IL-21.
  • Activation of neutrophils and natural killer cells – for example, IL-2, IL-8 and IL-12.
  • Produce detectable signs – interleukin-6 (IL-6) increases body temperature (fever) which inhibits microbial growth. IL-6, additionally, raises acute phase proteins such as CRP which is associated with inflammation
  • Promote vascular permeability, allowing faster recruitment of cells involved in immunity and causing swelling

Tumour Necrosis Factor

Tumour necrosis factor (TNF) is mainly produced by macrophages when they encounter an endotoxin. However, it can also be produced by other cells of the immune system including, mast cells, B cells and T cells. TNF α and β have similar functions, including:

  • Local induction of apoptosis.
  • Locally increasing vascular permeability.
  • Neutrophil chemotaxis.
  • Stimulation of a pro-inflammatory state – increased CRP production in the liver, increased production of prostaglandin E2 by macrophages and fever
  • Suppression of appetite.

High concentrations of TNF can induce shock through the increase in vascular permeability and resulting drop in blood pressure. On the other hand, chronic exposure to low levels leads to the syndrome of cachexia which is often seen in chronic infection and cancer.

Important Cytokines and Their Roles

Cytokine Main Source Main Actions
IL-1 α/ β Macrophages
  • Fever
  • T-cell activation
  •  Macrophage activation
IL-2 T helper 1 cells
  • T cell growth
  • B cell growth
  • NK cell growth
IL-4 T helper 2 cells
  •  Activation and growth of B cells
  •  Induces differentiation of CD4 T cells into T helper 2 cells
IL-6 Macrophages
  • Fever
  • Production of acute phase proteins
  •  Lymphocyte activation
  •  Stimulates antibody production
IL-8 Macrophages
  • Chemotaxis of neutrophils
  •  Activation of neutrophils
IL-10 T helper 2 cells

Macrophages

  • Inhibits immune function
IL-12 Macrophages
  •  Activation of NK cells
  • Induces differentiation of CD4 T cells into T helper 1 cells
IL-17 T helper 17 cells
  • Induces inflammatory response
  • Recruits neutrophils
Interferon-α T cells

B cells

Monocytes/Macrophages

  • Inhibits viral replication
Interferon-β T cells

B cells

Monocytes/Macrophages

  •  Inhibits viral replication
Interferon-γ T helper 1 cells

NK cells

  • Activation of macrophages
  •  Activation of NK cells
  •  Inhibits viral replication
  • Increases expression of MHC class I and II
  • Inhibits T helper 2 cells
TNF-α/β T helper cells

Macrophages

  • Activation of macrophages
  • Nitric oxide production
  • Induces inflammatory response
  •  Fever
  •  Shock

Clinical Relevance – Cytokine Therapy

Cytokines are important for promoting and modifying immune responses. Consequently, they are therapeutically administered in some conditions.

Interferons:

  • Hepatitis B and C to reduce risk of hepatocellular carcinoma
  • Chronic granulomatous disease to reduce risk of serious infection
  • Hairy cell leukaemia
  • Ovarian tumours

Interleukins:

  • Renal carcinoma
  • Melanoma

TNF:

  • Ovarian tumours