Inflammation

Inflammation can have a variety of triggers including:

• tissue damage, such as a burn or cut
• clot formation by platelets
• the presence of a foreign substance
• microbial infection
• some forms of cell death.

Inflammation begins with innate immune cells, such as neutrophils, being alerted to the trigger. This may be because damaged tissue has released ‘alert’ signals, or because the immune cell has detected microbial molecules such as bacterial cell wall components.

When activated, innate immune cells can immediately release a variety of inflammatory substances. These substances trigger the features of inflammation in nearby tissue, protecting the site and attracting an influx of additional immune cells. Different immune cell types, and inflammatory mediators are detected in acute and chronic inflammation.

Inflammatory mediators are typically short-lived. This serves to limit the duration of an inflammatory response. As soon as the trigger is removed, inflammation will normally diminish, preventing tissue damage.

Our research into how cells die has revealed that many of the molecules contributing to cell death have dual roles in inflammation, or are closely related to molecules functioning in inflammatory pathways.

Some types of cell death trigger inflammation. This ensures that the abnormal death of cells alerts immune cells to a potentially dangerous situation.

Inflammation is an important component of the innate immune response, which is the body’s first line of defense against infection. Inflammatory mediators enhance the responses of immune cells to potential infections, by:

• increasing blood flow and movement of immune cells into the inflamed tissue
• stimulating immune cells, such as triggering macrophages to be more likely to engulf nearby substances
• stimulating production of new immune cells through the release of colony stimulating factors

Inflammation is important for the generation of protective immunological memory. This ensures that repeat exposures to a microbe are rapidly dealt with by established immune cells that recognise the infectious agent.

Most vaccines include substances that trigger inflammation. These contribute to better immune responses, and longer-lasting immune protection.

Excessive or ongoing inflammation can cause pain and tissue damage, and prevent the normal functioning of the body’s organs.

Short-term, acute inflammation can be responsible for many of the symptoms of infections. These symptoms, such as fever, tend to assist the immune clearance of infection. Excessive or misplaced acute inflammation can cause severe illness or death.

Chronic inflammation is also associated with many diseases. Approximately one in three Australians has a chronic inflammatory disease, such as rheumatoid arthritis. These diseases place a significant social and economic burden on the community.

Chronic inflammation is triggered by ongoing immune responses. These immune responses can be against:

• a chronic infection that is not cleared. Chronic inflammation to the hepatitis B virus contributes to liver damage
• the body’s own tissue, such as joint tissue in rheumatoid arthritis.

In some conditions, such as rheumatic fever, inflammation begins in response to an infection by Streptococcus bacteria, but is redirected later to heart tissue, causing damage.

In many inflammatory diseases, symptoms can be greatly reduced in the short term by appropriate treatment. These include:

• corticosteroids that reduce immune cell function
• ‘non-steroidal’ anti-inflammatory medications that interfere with key molecules or cells contributing to the symptoms of inflammation
• targeted therapies that specifically inhibit the molecules that underpin inflammation or immune cell function
• these are showing great promise in improving the outlook for people with inflammatory diseases.

Compressing, immobilising and cooling the inflamed area can also improve the symptoms of inflammation, but do not eliminate the underlying cause of the inflammation.