Inflammation
Inflammation is the first response of the
immune system to
infection or
irritation and may be referred to as the
innate cascade. Inflammation is characterised by the following
quintet: redness (
rubor), heat (
calor),
swelling (
tumor),
pain (
dolor) and
dysfunction of the
organs involved (
functio laesa). The first four characteristics have been known since ancient times and are attributed to
Celsus;
functio laesa was added to the definition of inflammation by
Rudolf Virchow in 1858.
Inflammation has two main components -
cellular and
exudative.
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.
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.
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.
Various
leukocytes are involved in the initiation and maintenance of inflammation. These cells can be further stimulated to maintain inflammation through the action of adaptive cascade through
lymphocytes:
T cells,
B cells, and
antibodies. These inflammation 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.
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 specialised structures such as
hair or
sweat glands.
*
abscess formation - 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.
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.
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.
Inflammation is usually indicated by adding the suffix "
-itis", as shown below. However, some conditions such as
asthma do not follow this convention.
*
appendicitis:
appendix*
gastritis:
stomach*
laryngitis:
larynx*
meningitis:
meninges (the membrane covering the
brain)
*
otitis:
ear*
pancreatitis:
pancreasMore examples are available at
list of types of inflammation.
