Inflammation is the first response of the immune system to infection or irritation and may be referred to as the innate cascade. Inflammation is characterized 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.
Characteristics
The redness and heat are caused by the increased blood supply to the affected area. Blood vessels are vasodilated upstream of an infection while capillary permeability to the affected tissue is increased, resulting in a loss of blood plasma. Vasoconstriction downstream of the infection further increases edema or swelling. The swelling distends the tissues, compresses nerve endings, and thus causes pain. The white blood cells or leucocytes take on an important role in inflammation; they extravasate from the capillaries into tissue, and carry on 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, 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.
Leukocytes and cytokines
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:
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Mast cells which release histamine and prostaglandin in response to activation of stretch receptors. This is especially important in cases of trauma.
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Macrophages which release TNF-α, IL-1 in response to activation of toll-like receptors.
Resolution
When inflammation subsides, the damaged tissue is repaired. Depending on the severity of the inflammation and the type of tissue involved repairs may or may not be complete; in minor inflammations of the skin, for example, the tissue is capable of complete regeneration whereas in nervous tissue regeneration may be more limited and the damaged cells may be replaced with scar tissue.
Systemic 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 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. 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.
