Inflammation

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An abscess on the skin, showing the redness and swelling characteristic of inflammation. Black rings of necrotic tissue surround central areas of pus

An example of dermatitis, inflammation of the skin

Inflammation is the complex biological response of vascular tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective attempt by the organism to remove the injurous stimuli as well as initiate the healing process for the tissue.

In the absence of inflammation, wounds and infections would never heal and progressive destruction of the tissue would compromise the survival of the organism. However, inflammation which runs unchecked can also lead to a host of diseases, such as hay fever, atherosclerosis, and rheumatoid arthritis. It is for this reason that inflammation is normally tightly regulated by the body.

Inflammation is primarily achieved by the increased movement of plasma and white blood cells from the blood into the injured tissues, which normally act in concert as long as the injurous stimuli persist to maintain inflammation. A cascade of biochemical events propagates and matures the inflammatory response, and involves the local vascular system, the immune system, and various cells within the injured tissue.

Inflammation is not a synonym for infection. Even in cases where inflammation is caused by infection it is incorrect to use the terms as synonyms: infection is caused by an exogenous pathogen, while inflammation is the response of the organism to said pathogen.

1 Types
2 Cardinal signs
3 Characteristics
4 Leukocytes and cytokines
5 Outcomes
6 Systemic inflammation
- 6.1 Sepsis
- 6.2 Low-grade
7 Inflammation examples
8 See also
9 References
10 External links

[edit] Types

It has been suggested that Chronic inflammation be merged into this article or section. (Discuss)

Inflammation can be classified as either acute or chronic. Acute inflammation is a short term process which results in the classic signs of inflammation - swelling, redness, pain, heat, and loss of function - due to the infiltration of the tissues by plasma and leukocytes. It occurs as long as the injurous stimuli is present and ceases once the stimuli has been removed, broken down, or walled off by scarring (fibrosis). Chronic inflammation is a pathlogical condition characterised by concurrent active inflammation, tissue destruction, and attempts at repair.

The two types of inflammation demonstrate the double-edged nature inherant to the process. Removal of harmful stimuli often involves the production of compounds toxic to the body, and the resultant scarring permanently impairs the original function of the tissue. If left unchecked, a chronic state of inflammation leads to the pathological cycle of destruction and healing by the tissue.

[edit] Cardinal signs

Acute inflammation is characterised by the following quintet:

Redness (rubor)
Heat (calor)
Swelling (tumor)
Pain (dolor)
Dysfunction of the tissue involved (functio laesa).

The first four characteristics have been known since ancient times and are attributed to Celsus. Loss of function was added to the definition of inflammation by Rudolf Virchow in 1858. These signs are directly and indirectly attributable to the influx of blood and blood products into the affected area.

Chronic inflammation is not characterised by the cardinal signs listed above. Instead, chronically inflamed tissue is characterised by the infiltration of mononuclear immune cells (monocytes, macrophages, lymphocytes, and plasma cells), tissue destruction, and attempts at healing, which include angiogenesis and fibrosis.

[edit] Characteristics

Inflammation has two main components: cellular and exudative.

The cellular component involves the movement of white blood cells from blood vessels into the inflamed tissue. The white blood cells, or leukocytes, take on an important role in inflammation; they extravasate (filter out) from the capillaries into tissue, and act as phagocytes, picking up bacteria and cellular debris. They may also aid by walling off an infection and preventing its spread.

The exudative component involves the movement of fluid, usually containing many important proteins such as fibrin and immunoglobulins (antibodies). Blood vessels are dilated upstream of an infection (causing redness and heat) and constricted downstream while capillary permeability to the affected tissue is increased, resulting in a net loss of blood plasma into the tissue, giving rise to edema or swelling. The swelling distends the tissues, compresses nerve endings, and thus causes pain. Inflammation can be recognized by nitric oxide.

If inflammation of the affected site persists, released cytokines IL-1 and TNF will activate endothelial cells to upregulate receptors VCAM-1, ICAM-1, E-selectin, and L-selectin for various immune cells. Receptor upregulation increases extravasation of neutrophils, monocytes, activated T-helper and T-cytotoxic, and memory T and B cells to the infected site.

Neutrophils are characteristic of inflammation in the early stages. They are the first cells to appear in an infected area, and any section of recently inflamed (within a couple of days or so) tissue viewed under a microscope will appear packed with them. They are easily identified by their multilobed nuclei and granular cytoplasm and perform many important functions, including phagocytosis and the release of extracellular chemical messengers. Neutrophils only live for a couple days in these interstitial areas, so if the inflammation persists for a longer duration then they are gradually replaced by longer lived monocytes.

[edit] Leukocytes and cytokines

Various leukocytes are involved in the initiation and maintenance of inflammation. Generally speaking, acute inflammation is mediated by granulocytes or polymorphonuclear leukocytes, while chronic inflammation is mediated by mononuclear cells such as monocytes and macrophages. These cells can be further stimulated to maintain inflammation through the action of an adaptive cascade involving lymphocytes: T cells, B cells, and antibodies. These inflammatory cells are:

Mast cells which release histamine and prostaglandin in response to activation of stretch receptors. This is especially important in cases of trauma.
Macrophages which release TNF-α, IL-1 in response to activation of toll-like receptors.

[edit] Outcomes

The outcome in a particular circumstance will be determined by the tissue in which the injury has occurred and the injurious agent that is causing it.

There are four possible results to inflammation:

Resolution, the complete reconstitution of damaged tissue, does not usually occur in the body.
Connective tissue scarring. Some 24 hours after inflammation in a wound first occurs, the wound healing response will commence. This response involves the formation of connective tissue to bridge the gap caused by injury and the process of angiogenesis, the formation of new blood vessels, to provide nutrients to the newly formed tissue. Often healing can not occur completely and a scar will form; for example after laceration to the skin, a connective tissue scar results which does not contain any specialized structures such as hair or sweat glands.
Abscess formation is found primarily in infections by pyogenic bacteria.
Ongoing or chronic inflammation. If the injurious agent continues, chronic inflammation will ensue. This process, marked by inflammation lasting many days, months or even years, may lead to the formation of a chronic wound. Chronic inflammation is characterised by a dominating presence of macrophages in the injured tissue, which extravasate via the same methods discussed above (ICAM-1 VCAM-1). These cells are powerful defensive agents of the body, but the toxins they release (including reactive oxygen species) are injurious to the organism's own tissues as well as invading agents. This is why chronic inflammation is almost always accompanied by tissue destruction. Finally, an abscess, or a collection of pus, can form in chronic inflammation.

[edit] Systemic inflammation

[edit] Sepsis

When inflammation overwhelms the whole organism, systemic inflammatory response syndrome (SIRS) is diagnosed. When it is due to infection, the term sepsis is applied. Vasodilation and organ dysfunction are serious problems that may lead to septic shock and death.

[edit] Low-grade

With the discovery of interleukins, another concept of systemic inflammation developed. Although the processes involved are identical, this form of inflammation is not confined to a particular tissue but involves the endothelium (lining of blood vessels) and many other organ systems. High levels of several inflammation-related markers such as IL-6, IL-8, and TNF-α are associated with obesity.^[1]^[2]

These levels are reduced in association with increased levels of antiinflammatory molecules within four weeks after patients begin a very low calorie diet.^[3]. The role of systemic inflammation as a cause and/or result of insulin resistance and atherosclerosis is the subject of intense research. It has little direct bearing on clinical care.

[edit] Inflammation examples

Inflammation is usually indicated by adding the suffix "-itis", as shown below. However, some conditions such as asthma and pneumonia do not follow this convention.