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Inflammation


Description

Inflammation is the first response of the immune system to infection or irritation.

Inflammation is characterized by the following four: 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 may be referred to as the innate cascade. It 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 filter ou (extravasatet) 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. Phagocytes are leukocytes (white blood cells) that engulf invading micro-organisms, and then kill them.



If inflammation of the affected site persists, released cytokines IL-1(interleukin-1) and TNF (tumor necrosis factor) will activate endothelial cells to up-regulate receptors VCAM-1 (vascular cell adhesion molecule 1), ICAM-1 ( intercellular adhesion molecule 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.

Causes

Inflammation is the first response of the immune system to infection or irritation. Inflammation can be acute, as occurs after a physical injury, or chronic. There are several causes of chronic inflammation, including: Persistent infections; Prolonged exposure to toxic elements; and Autoimmune disease.

Inflammation is a protective response of the body that occurs during the process of repair. The Russian biologist Elie Metchnikoff, proposed that the purpose of inflammation was to bring phagocytotic cells to the injured area in order to engulf invading bacteria. Both Metchnikoff and Paul Ehrlich (who developed the humoral theory of immunity) shared the Nobel Prize in 1908.



A new theory has been published by Dr. Martin L. Pall (Professor of Biochemistry and Basic Medical Sciences at Washington State University). The theory involves a chain of events:

¥ Chronic infections act to induce excessive production of inflammatory cytokines.

¥ Inflammatory cytokines induce nitric oxide synthase (iNOS) which synthesizes excessive amounts of nitric oxide

¥ Nitric oxide reacts with superoxide to produce the potent oxidant peroxynitrite (nitrogen dioxide).

¥ Peroxynitrite acts to increase the levels of both nitric oxide and superoxide which react to produce more peroxynitrite

In this way, once peroxynitrite levels are elevated, they may act to continue the elevation, thus producing a self-sustaining vicious cycle.



Conventional Labs

Erythrocyte Sedimentation Rate (ESR) is a conventional marker of inflammation.

C-reactive protein (CRP) is a sensitive marker of inflammation.

Inflammatory cytokines include: Tumor Necrosis Factor-alpha, Interleukin-6, Interleukin 1 beta, and Leukotriene B(4). These are rarely ordered due to their high costs.

 

 

 

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