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Inflammation is a response of a tissue to injury, often injury caused by invading pathogens. It is characterized by

A bacterial infection initiates inflammation through several interconnecting mechanisms:

Mast Cells

Mast cells are found in the tissues.

Mast cells appear to be key players in the initiation of inflammation. Activated mast cells release literally dozens of potent mediators; These mediators are active in either (or, in some cases, both)

I shall not attempt to catalog all the players, but here are some of the major (and best understood) ones.

Tumor Necrosis Factor-alpha (TNF-α)

Large amounts of TNF-α are quickly released by stimulated mast cells. All the cells involved in inflammation have receptors for TNF-α and are activated by it to synthesize more on their own. This positive feedback quickly amplifies the response.

Link to a description of how the binding of TNF-α to its receptors on a responding cell initiates new gene transcription by the cell.


Tryptase is the most abundant protein released by mast cells. It is a serine protease. Like the mammalian enzyme trypsin, tryptase cleaves peptide bonds on the C-terminal side of arginines and lysines. It activates C3 of the complement system and probably supports inflammation in other ways as well.


These are chemotactic cytokines; that is, secreted proteins that attract other leukocytes into the area. Several have been identified.

Reactive Oxygen Species (ROS)

These are produced by activated phagocytes: macrophages and neutrophils. They are toxic for microorganisms but can also lead to tissue injury. ROS are described in detail on another page. Link to it.


The granules of mast cells are loaded with histamine and their exocytosis releases this potent mediator. Histamine increases the blood flow to the area and the leakage of fluid and proteins from the blood into the tissue space. Thus the quick release of histamine produces the redness and swelling associated with inflammation.

Interleukin-1 (IL-1)

Macrophages, monocytes, and activated platelets are sources of this cytokine. IL-1 has both

IL-1 causes fever by stimulating the release of prostaglandins, which act on the temperature control center of the hypothalamus.


IL-1 is synthesized from a larger precursor that is cleaved by a caspase (caspase-1). Caspase-1 is part of a multi-protein complex in the cytosol of macrophages and neutrophils called an inflammasome. Inflammasomes are activated by several different products produced by invading bacteria. Some of these are first "seen" by toll-like receptors (TLRs) thus providing a link between the innate immune system and inflammation.


Bradykinin is a nonapeptide (9 amino acids).

It is synthesized by proteolytic cleavage of an inactive precursor (a kininogen) that is produced by the liver and circulates at all times in the blood (one of the alpha-globulins).

Bradykinin The process: Bradykinin also

Prostaglandins and Leukotrienes

These potent mediators of inflammation are derivatives of arachidonic acid (AA) a 20-carbon unsaturated fatty acid produced from membrane phospholipids.

The principal pathways of arachidonic acid metabolism are

Acute Inflammation: The Good Side of Inflammation

The acute inflammatory response to tissue damage is of great value. By

inflammation protects the body.

Its importance is demonstrated by the problems people with inherited defects in components of the process have with infections.

Some examples:

Chronic Inflammation: The Bad Side of Inflammation

In chronic inflammation, the inflammatory response is out of proportion to the threat it is faced with or is directed against inappropriate targets. In the first case, the result can be more damage to the body than the agent itself would have produced.

Allergies and Autoimmune Diseases

are examples of inflammation in response to what should have been a harmless agent.

Some examples:

In many of these cases, the problem is made worse by the formation of antibodies against The antibodies complex with the antigens triggering the complement system with all its mediators of inflammation.

The result: immune complex disorders.

Link to a discussion of several immune complex disorders.

Treating Inflammation

Inappropriate inflammation can be treated with

NonSteroidal Anti-Inflammatory Drugs (NSAIDs)

The NSAIDs achieve their effects by blocking the activity of cyclooxygenases.

The body produces two different forms of cyclooxygenase: In addition to reducing the fever and pain of inflammation, NSAIDs also inhibit clotting. They do this by interfering with the synthesis of thromboxane A2 in platelets. This is the reason that But regular use of NSAIDs has a downside: a tendency to develop ulcers in the stomach and duodenum.

Most of the NSAIDs inhibit both COX-1 and COX-2. However, some newer drugs, the so-called COX-2 inhibitors, such as

are much more active against COX-2 than COX-1.

COX-2 inhibitors are effective against inflammation and avoid damage to the GI tract. But, unfortunately, they increase the risk of blood clots — which can cause heart attacks and strokes — because they do not block the synthesis of thromboxane A2 by platelets (which contain only COX-1). So people depending on NSAIDs for their heart protective effects must monitor any use of COX-2 inhibitors carefully.

In fact, because of the increased risk of heart attacks and strokes, the manufacturer of Vioxx® removed it from the market on 30 September 2004.

Therapeutic Proteins

Recombinant DNA and monoclonal antibody technology have produced some new therapies that are being enlisted in the battle against damaging inflammation.

In fact, all the more powerful anti-inflammatory agents (e.g., glucocorticoids) increase the risk of infection.

Sepsis and Septic Shock

On occasions, for reasons that are not entirely clear, the inflammatory response — usually to an infection by lipopolysaccharide (LPS)-bearing Gram-negative bacteria — spirals out of control progressing until it involves the entire body. This life-threatening development is called sepsis.

The circulatory system loses its integrity: If these responses are massive, they can lead to septic shock

Toxic Shock Syndrome

Some Gram-positive cocci can produce a similar condition, but here the eliciting agent is not LPS but a toxin liberated by the bacteria.

In theory, anti-inflammatory agents should be useful in combating sepsis. But so far, only recombinant protein C has shown any promise (by inhibiting the formation of thrombin), and severe bleeding is a dangerous side-effect.

Inflammation and Cancer

Chronic inflammation is also a frequent cause of cancer.

Read more in Bruce Ames's The Causes and Prevention of Cancer
The strong link between chronic inflammation and cancer should not be surprising when you consider that
Two Related Links:
Allergies and inflammation
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9 November 2013