Inflammation (from Latin: inflammatio) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants.[1][2] The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin calor, dolor, rubor, tumor, and functio laesa).
Inflammation is a generic response, and therefore is considered a mechanism of innate immunity, whereas adaptive immunity is specific to each pathogen.[3]
Inflammation is a protective response involving immune cells, blood vessels, and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out damaged cells and tissues, and initiate tissue repair. Too little inflammation could lead to progressive tissue destruction by the harmful stimulus (e.g. bacteria) and compromise the survival of the organism. However inflammation can also have negative effects.[4] Too much inflammation, in the form of chronic inflammation, is associated with various diseases, such as hay fever, periodontal disease, atherosclerosis, and osteoarthritis.
Inflammation can be classified as acute or chronic. Acute inflammation is the initial response of the body to harmful stimuli, and is achieved by the increased movement of plasma and leukocytes (in particular granulocytes) from the blood into the injured tissues. A series of biochemical events propagates and matures the inflammatory response, involving the local vascular system, the immune system, and various cells in the injured tissue. Prolonged inflammation, known as chronic inflammation, leads to a progressive shift in the type of cells present at the site of inflammation, such as mononuclear cells, and involves simultaneous destruction and healing of the tissue.
Inflammation has also been classified as Type 1 and Type 2 based on the type of cytokines and helper T cells (Th1 and Th2) involved.[5]
The earliest known reference for the term inflammation is around the early 15th century. The word root comes from Old French inflammation around the 14th century, which then comes from Latin inflammatio or inflammationem. Literally, the term relates to the word "flame", as the property of being "set on fire" or "to burn".[6]
The term inflammation is not a synonym for infection. Infection describes the interaction between the action of microbial invasion and the reaction of the body's inflammatory response—the two components are considered together in discussion of infection, and the word is used to imply a microbial invasive cause for the observed inflammatory reaction. Inflammation, on the other hand, describes just the body's immunovascular response, regardless of cause. But, because of the two are often correlated, words ending in the suffix -itis (which means inflammation) are sometimes informally described as referring to infection: for example, the word urethritis strictly means only "urethral inflammation", but clinical health care providers usually discuss urethritis as a urethral infection because urethral microbial invasion is the most common cause of urethritis. However, the inflammation–infection distinction is crucial in situations in pathology and medical diagnosis that involve inflammation that is not driven by microbial invasion, such as cases of atherosclerosis, trauma, ischemia, and autoimmune diseases (including type III hypersensitivity).
Biological:
Chemical:[7]
Psychological:
Acute inflammation is a short-term process, usually appearing within a few minutes or hours and begins to cease upon the removal of the injurious stimulus.[10] It involves a coordinated and systemic mobilization response locally of various immune, endocrine and neurological mediators of acute inflammation. In a normal healthy response, it becomes activated, clears the pathogen and begins a repair process and then ceases.[11]
Acute inflammation occurs immediately upon injury, lasting only a few days.[12] Cytokines and chemokines promote the migration of neutrophils and macrophages to the site of inflammation.[12] Pathogens, allergens, toxins, burns, and frostbite are some of the typical causes of acute inflammation.[12] Toll-like receptors (TLRs) recognize microbial pathogens.[12] Acute inflammation can be a defensive mechanism to protect tissues against injury.[12] Inflammation lasting 2–6 weeks is designated subacute inflammation.[12][13]
Inflammation is characterized by five cardinal signs,[16][17] (the traditional names of which come from Latin):
The first four (classical signs) were described by Celsus (c. 30 BC–38 AD).[19]
Pain is due to the release of chemicals such as bradykinin and histamine that stimulate nerve endings.[16] (Acute inflammation of the lung (usually as in response to pneumonia) does not cause pain unless the inflammation involves the parietal pleura, which does have pain-sensitive nerve endings.[16]) Heat and redness are due to increased blood flow at body core temperature to the inflamed site. Swelling is caused by accumulation of fluid.
The fifth sign, loss of function, is believed to have been added later by Galen,[20] Thomas Sydenham[21] or Rudolf Virchow.[10][16][17] Examples of loss of function include pain that inhibits mobility, severe swelling that prevents movement, having a worse sense of smell during a cold, or having difficulty breathing when bronchitis is present.[22][23] Loss of function has multiple causes.[16]
The process of acute inflammation is initiated by resident immune cells already present in the involved tissue, mainly resident macrophages, dendritic cells, histiocytes, Kupffer cells and mast cells. These cells possess surface receptors known as pattern recognition receptors (PRRs), which recognize (i.e., bind) two subclasses of molecules: pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). PAMPs are compounds that are associated with various pathogens, but which are distinguishable from host molecules. DAMPs are compounds that are associated with host-related injury and cell damage.
At the onset of an infection, burn, or other injuries, these cells undergo activation (one of the PRRs recognize a PAMP or DAMP) and release inflammatory mediators responsible for the clinical signs of inflammation. Vasodilation and its resulting increased blood flow causes the redness (rubor) and increased heat (calor). Increased permeability of the blood vessels results in an exudation (leakage) of plasma proteins and fluid into the tissue (edema), which manifests itself as swelling (tumor). Some of the released mediators such as bradykinin increase the sensitivity to pain (hyperalgesia, dolor). The mediator molecules also alter the blood vessels to permit the migration of leukocytes, mainly neutrophils and macrophages, to flow out of the blood vessels (extravasation) and into the tissue. The neutrophils migrate along a chemotactic gradient created by the local cells to reach the site of injury.[10] The loss of function (functio laesa) is probably the result of a neurological reflex in response to pain.
In addition to cell-derived mediators, several acellular biochemical cascade systems—consisting of preformed plasma proteins—act in parallel to initiate and propagate the inflammatory response. These include the complement system activated by bacteria and the coagulation and fibrinolysis systems activated by necrosis (e.g., burn, trauma).[10]
Acute inflammation may be regarded as the first line of defense against injury. Acute inflammatory response requires constant stimulation to be sustained. Inflammatory mediators are short-lived and are quickly degraded in the tissue. Hence, acute inflammation begins to cease once the stimulus has been removed.[10]
Chronic inflammation is inflammation that lasts for months or years.[13] Macrophages, lymphocytes, and plasma cells predominate in chronic inflammation, in contrast to the neutrophils that predominate in acute inflammation.[13] Diabetes, cardiovascular disease, allergies, and chronic obstructive pulmonary disease (COPD) are examples of diseases mediated by chronic inflammation.[13] Obesity, smoking, stress and insufficient diet are some of the factors that promote chronic inflammation.[13] A 2014 study reported that 60% of Americans had at least one chronic inflammatory condition, and 42% had more than one.[13]
Common signs and symptoms that develop during chronic inflammation are:[13]
As defined, acute inflammation is an immunovascular response to inflammatory stimuli, which can include infection or trauma.[25][26] This means acute inflammation can be broadly divided into a vascular phase that occurs first, followed by a cellular phase involving immune cells (more specifically myeloid granulocytes in the acute setting).[25] The vascular component of acute inflammation involves the movement of plasma fluid, containing important proteins such as fibrin and immunoglobulins (antibodies), into inflamed tissue.
Upon contact with PAMPs, tissue macrophages and mastocytes release vasoactive amines such as histamine and