messengers important in inflammation

Chapter 8 Chemical messengers important in inflammation

There are many chemicals important in inflammation. They are linked in a complex web of feedback mechanisms that control the inflammatory response. These chemicals can be divided into endogenous mediators that are produced by cells within the tissues and plasma proteins that circulate in the bloodstream.

Endogenous chemical mediators

The chemical mediators can either be released from granules where they are preformed and stored (e.g. histamine) or be synthesized on demand (e.g. the arachadonic acid derivatives prostaglandins, leukotrienes and lipoxins)

Histamine is mostly released from granules in mast cells, although eosinophils and platelets also contain some. Mast cells appear to be derived from circulating basophils, which are very similar cells. Histamine causes vascular dilatation and increased vascular permeability. It is quick acting and, therefore, it is important in acute inflammation.

Serotonin (5-hydroxytryptamine) is similar to histamine, but in humans it is found in platelets rather than mast cells.

Prostaglandins are a group of compounds having a range of effects; some increase vascular permeability, others induce platelet aggregation. The non-steroidal anti-inflammatory drugs (NSAIDs) inhibit enzymes involved in prostaglandin synthesis.

Leukotrienes are powerful chemotactic agents and cause vasoconstriction and leukocyte adhesion, and chemotaxis and activation of neutrophils and macrophages.

Lipoxins are arachadonic acid derivatives and have anti-inflammatory effects, tending to inhibit leukocyte activity.

Nitric oxide is a potent vasodilator and it also inhibits rolling and adhesion of leukocytes. It is synthesized by endothelial and inflammatory cells in response to cytokine stimulation.

Cytokines are a superfamily of inflammatory mediators produced at a site of injury and include interleukins (IL), interferons, colony-stimulating factors, growth factors, tumour necrosis factors (TNF) and chemokines.


The term cytokine is used for inflammatory mediators produced at a site of injury or inflammation that are not stored as preformed substances or prohormones but are produced when required via transcription and translation of the relevant genes. They are polypeptides or glycoproteins of low molecular weight and act by binding to receptors of target cells, generally affecting gene transcription via second messengers. Cytokines can be divided into a number of groups depending on their principal functions, but many have multiple roles and could be included in several different groups. Some, like TNF-α activate phagocytes, while others, like IL-2 and transforming growth factor (TGF) beta regulate lymphocyte growth, differentiation and activity. The chemokines are cytokines with chemoattractant properties and are responsible for the migration of inflammatory cells by chemotaxis; they can also activate leukocytes. Cytokines can have autocrine, paracrine or endocrine effects; an example of the last is the fever that accompanies inflammation.

A useful way of thinking about cytokines is to divide them into pro-inflammatory cytokines (e.g. TNF-α, IL-1, IL-2, IL-6) that upregulate inflammatory responses, and anti-inflammatory cytokines (e.g. IL-4, IL-10 and TGF-β) that act as a brake on inflammation and actively terminate the process. However, because of the complex nature of inflammation control, some cytokines can be pro-inflammatory in some circumstances and anti-inflammatory in others. Therapeutic manipulation of cytokines has the potential to help patients with a wide variety of inflammatory diseases, and research in this area has resulted in drugs such as infliximab, an antibody directed against TNF-α. Infliximab and related drugs inhibit TNF-α and can be used to treat conditions such as Crohn’s disease and rheumatoid arthritis.

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Jul 3, 2016 | Posted by in MUSCULOSKELETAL MEDICINE | Comments Off on messengers important in inflammation

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