5th February 2024

Types of inflammatory mediators

Inflammatory mediators drive the inflammatory process. These include proteins, glycoproteins, vasoactive amines, cytokines, prostaglandins, leukotrienes, nitrous oxide, and oxygen-free radicals. Inflammatory mediators are released by specialised inflammatory cells such as macrophages, neutrophils and lymphocytes.

Vasoactive amines

Histamine is a vasoactive amine involved in immune responses. It is produced and stored by basophils and mast cells. These cells can be stimulated by antigens or allergens through IgE antibodies found in their cell membrane, causing degranulation and release of histamine. Histamine then acts on specific receptors to cause specialised responses, including vasodilation and increased vascular permeability. Histamine also has many other functions alongside its role within the inflammatory cascade.

Serotonin is another vasoactive amine that has many functions as a neurotransmitter.

Cytokines

Cytokines are a group of proteins whose actions can be determined through etymology – ‘cyto’ and ‘kinesis,’ the Greek words for cell and movement. Cytokines are secreted by immune cells and act on other cells to direct their movement and action through the inflammatory cascade. Important cytokines to be aware of include interleukins, interferons, tumour necrosis factor, chemokines and transforming growth factor.

Interleukins are synthesised and released by leucocytes, mainly CD4 helper T lymphocytes. Interleukins regulate immune and inflammatory responses as well as haematopoiesis. There are over fifty different interleukins with pro- and anti-inflammatory functions.

Interferons are cytokines released by cells in response to viral infection. Tumour necrosis factor (TNF) is a pro-inflammatory cytokine. Macrophages and eosinophils secrete TNF-a to recruit T lymphocytes. Transforming growth factor (TGF) controls the repair of damaged tissue. It is released by platelets and signals white blood cells (including T lymphocytes) and fibroblasts to approach.

Prostaglandins and leukotrienes

Prostaglandins are lipid molecules derived from arachidonic acid, known as eicosanoids, that act on various receptors to cause vasodilation, systemic fever and pain. Inhibition of prostaglandin action has particular significance in the pharmacology of reducing inflammation and its symptoms.

Leukotrienes are also eicosanoids that trigger inflammatory processes, such as the chemotaxis of neutrophils to sites of injury and stimulation of cytokine production. Similar to histamine, leukotrienes also take effect in the respiratory smooth muscle, resulting in bronchoconstriction.

References

• Kushner I. Acute phase reactants. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA: UpToDate Inc. http://www.uptodate.com
• Nicrovic PA. The autoinflammatory diseases: An overview. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA: UpToDate Inc. http://www.uptodate.com
• Castells MC, Bankova L. Mast cell-derived mediators. In: UpToDate, Post TW (Ed), UpToDate, Waltham, MA: UpToDate Inc. http://www.uptodate.com
• White M. Mediators of inflammation and the inflammatory process. J Allergy Clin Immunol. 1999 Mar;103(3 Pt 2):S378-81. doi: 10.1016/s0091-6749(99)70215-0. PMID: 10069896.
• Abdulkhaleq LA, Assi MA, Abdullah R, Zamri-Saad M, Taufiq-Yap YH, Hezmee MNM. The crucial roles of inflammatory mediators in inflammation: A review. Vet World. 2018 May;11(5):627-635. doi 10.14202/vetworld.2018.627-635. Epub 2018 May 15. PMID: 29915501; PMCID: PMC5993766.