|Symptoms||Heat, pain, redness, swelling|
|Complications||Asthma, pneumonia, autoimmune diseases|
|Duration||acute Few days chronic Up to many months, or years|
Inflammation (from Latin: ) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants, and 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 necrotic cells and tissues damaged from the original insult and the inflammatory process, 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.
Inflammation can be classified as either 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 (especially granulocytes) from the blood into the injured tissues.
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 is characterized by simultaneous destruction and healing of the tissue from the inflammatory process.
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 when discussing an infection, and the word is used to imply a microbial invasive cause for the observed inflammatory reaction.
Inflammation, on the other hand, describes purely the body's immunovascular response, whatever the cause may be.
But because of how often the two are correlated, words ending in the suffix (which refers to 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.
It is useful to differentiate inflammation and infection because there are typical situations in pathology and medical diagnosis where inflammation is not driven by microbial invasion – for example, atherosclerosis, trauma, ischemia, and autoimmune diseases including type III hypersensitivity.
|Causative agent||Bacterial pathogens, injured tissues||Persistent acute inflammation due to non-degradable pathogens, viral infection, persistent foreign bodies, or autoimmune reactions|
|Major cells involved||neutrophils (primarily), basophils (inflammatory response), and eosinophils (response to helminth worms and parasites), mononuclear cells (monocytes, macrophages)||Mononuclear cells (monocytes, macrophages, lymphocytes, plasma cells), fibroblasts|
|Primary mediators||Vasoactive amines, eicosanoids||IFN-γ and other cytokines, growth factors, reactive oxygen species, hydrolytic enzymes|
|Duration||Few days||Up to many months, or years|
|Outcomes||Resolution, abscess formation, chronic inflammation||Tissue destruction, fibrosis, necrosis|
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.
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.
It is characterized by five cardinal signs:
An acronym that may be used to remember the key symptoms is "PRISH", for pain, redness, immobility (loss of function), swelling and heat.
The traditional names for signs of inflammation come from Latin:
Redness and heat are due to increased blood flow at body core temperature to the inflamed site; swelling is caused by accumulation of fluid; pain is due to the release of chemicals such as bradykinin and histamine that stimulate nerve endings.
Loss of function has multiple causes.
Process of acute inflammation
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).
The neutrophils migrate along a chemotactic gradient created by the local cells to reach the site of injury.
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.
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.
Vasodilation and increased permeability
As defined, acute inflammation is an immunovascular response to an inflammatory stimulus.
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).
Upon contact with PAMPs, tissue macrophages and mastocytes release vasoactive amines such as histamine and serotonin, as well as eicosanoids such as prostaglandin E2 and leukotriene B4 to remodel the local vasculature.
Macrophages and endothelial cells release nitric oxide.
The increased collection of fluid into the tissue causes it to swell (edema).
This exuded tissue fluid contains various antimicrobial mediators from the plasma such as complement, lysozyme, antibodies, which can immediately deal damage to microbes, and opsonise the microbes in preparation for the cellular phase.
These clotting mediators also provide a structural staging framework at the inflammatory tissue site in the form of a fibrin lattice – as would construction scaffolding at a construction site – for the purpose of aiding phagocytic debridement and wound repair later on.
Acute inflammation is characterized by marked vascular changes, including vasodilation, increased permeability and increased blood flow, which are induced by the actions of various inflammatory mediators.
Increased permeability of the vessels results in the movement of plasma into the tissues, with resultant stasis due to the increase in the concentration of the cells within blood – a condition characterized by enlarged vessels packed with cells.
Normal flowing blood prevents this, as the shearing force along the periphery of the vessels moves cells in the blood into the middle of the vessel.
Plasma cascade systems
- The complement system, when activated, creates a cascade of chemical reactions that promotes opsonization, chemotaxis, and agglutination, and produces the MAC.
- The kinin system generates proteins capable of sustaining vasodilation and other physical inflammatory effects.
- The coagulation system or clotting cascade, which forms a protective protein mesh over sites of injury.
- The fibrinolysis system, which acts in opposition to the coagulation system, to counterbalance clotting and generate several other inflammatory mediators.
- non-exhaustive list
|Bradykinin||Kinin system||A vasoactive protein that is able to induce vasodilation, increase vascular permeability, cause smooth muscle contraction, and induce pain.|
|C3||Complement system||Cleaves to produce C3a and C3b. C3a stimulates histamine release by mast cells, thereby producing vasodilation. C3b is able to bind to bacterial cell walls and act as an opsonin, which marks the invader as a target for phagocytosis.|
|C5a||Complement system||Stimulates histamine release by mast cells, thereby producing vasodilation. It is also able to act as a chemoattractant to direct cells via chemotaxis to the site of inflammation.|
|Factor XII (Hageman Factor)||Liver||A protein that circulates inactively, until activated by collagen, platelets, or exposed basement membranes via conformational change. When activated, it in turn is able to activate three plasma systems involved in inflammation: the kinin system, fibrinolysis system, and coagulation system.|
|Membrane attack complex||Complement system||A complex of the complement proteins C5b, C6, C7, C8, and multiple units of C9. The combination and activation of this range of complement proteins forms the membrane attack complex, which is able to insert into bacterial cell walls and causes cell lysis with ensuing bacterial death.|
|Plasmin||Fibrinolysis system||Able to break down fibrin clots, cleave complement protein C3, and activate Factor XII.|
|Thrombin||Coagulation system||Cleaves the soluble plasma protein fibrinogen to produce insoluble fibrin, which aggregates to form a blood clot. Thrombin can also bind to cells via the PAR1 receptor to trigger several other inflammatory responses, such as production of chemokines and nitric oxide.|
The cellular component involves leukocytes, which normally reside in blood and must move into the inflamed tissue via extravasation to aid in inflammation.
Others release enzymatic granules that damage pathogenic invaders.
Leukocytes also release inflammatory mediators that develop and maintain the inflammatory response.
Main article: Leukocyte extravasation
Various leukocytes, particularly neutrophils, are critically involved in the initiation and maintenance of inflammation.
These cells must be able to move to the site of injury from their usual location in the blood, therefore mechanisms exist to recruit and direct leukocytes to the appropriate place.
The process of leukocyte movement from the blood to the tissues through the blood vessels is known as extravasation, and can be broadly divided up into a number of steps:
- Leukocyte margination and endothelial adhesion: The white blood cells within the vessels which are generally centrally located move peripherally towards the walls of the vessels. Activated macrophages in the tissue release cytokines such as IL-1 and TNFα, which in turn leads to production of chemokines that bind to proteoglycans forming gradient in the inflamed tissue and along the endothelial wall. Inflammatory cytokines induce the immediate expression of P-selectin on endothelial cell surfaces and P-selectin binds weakly to carbohydrate ligands on the surface of leukocytes and causes them to "roll" along the endothelial surface as bonds are made and broken. Cytokines released from injured cells induce the expression of E-selectin on endothelial cells, which functions similarly to P-selectin. Cytokines also induce the expression of integrin ligands such as ICAM-1 and VCAM-1 on endothelial cells, which mediate the adhesion and further slow leukocytes down. These weakly bound leukocytes are free to detach if not activated by chemokines produced in injured tissue after signal transduction via respective G protein-coupled receptors that activates integrins on the leukocyte surface for firm adhesion. Such activation increases the affinity of bound integrin receptors for ICAM-1 and VCAM-1 on the endothelial cell surface, firmly binding the leukocytes to the endothelium.
- Migration across the endothelium, known as transmigration, via the process of diapedesis: Chemokine gradients stimulate the adhered leukocytes to move between adjacent endothelial cells. The endothelial cells retract and the leukocytes pass through the basement membrane into the surrounding tissue using adhesion molecules such as ICAM-1.
- Movement of leukocytes within the tissue via chemotaxis: Leukocytes reaching the tissue interstitium bind to extracellular matrix proteins via expressed integrins and CD44 to prevent them from leaving the site. A variety of molecules behave as chemoattractants, for example, C3a or C5, and cause the leukocytes to move along a chemotactic gradient towards the source of inflammation.
Main article: Phagocyte
Extravasated neutrophils in the cellular phase come into contact with microbes at the inflamed tissue.
Most PAMPs that bind to endocytic PRRs and initiate phagocytosis are cell wall components, including complex carbohydrates such as mannans and β-glucans, lipopolysaccharides (LPS), peptidoglycans, and surface proteins.
Upon endocytic PRR binding, actin-myosin cytoskeletal rearrangement adjacent to the plasma membrane occurs in a way that endocytoses the plasma membrane containing the PRR-PAMP complex, and the microbe.
Phosphatidylinositol and Vps34-Vps15-Beclin1 signalling pathways have been implicated to traffic the endocytosed phagosome to intracellular lysosomes, where fusion of the phagosome and the lysosome produces a phagolysosome.
Phagocytic efficacy can be enhanced by opsonization.
Plasma derived complement C3b and antibodies that exude into the inflamed tissue during the vascular phase bind to and coat the microbial antigens.
The co-stimulation of endocytic PRR and opsonin receptor increases the efficacy of the phagocytic process, enhancing the lysosomal elimination of the infective agent.
- non-exhaustive list
|Lysosome granules||Enzymes||Granulocytes||These cells contain a large variety of enzymes that perform a number of functions. Granules can be classified as either specific or azurophilic depending upon the contents, and are able to break down a number of substances, some of which may be plasma-derived proteins that allow these enzymes to act as inflammatory mediators.|
|Histamine||Monoamine||Mast cells and basophils||Stored in preformed granules, histamine is released in response to a number of stimuli. It causes arteriole dilation, increased venous permeability, and a wide variety of organ-specific effects.|
|IFN-γ||Cytokine||T-cells, NK cells||Antiviral, immunoregulatory, and anti-tumour properties. This interferon was originally called macrophage-activating factor, and is especially important in the maintenance of chronic inflammation.|
|IL-8||Chemokine||Primarily macrophages||Activation and chemoattraction of neutrophils, with a weak effect on monocytes and eosinophils.|
|Leukotriene B4||Eicosanoid||Leukocytes, cancer cells||Able to mediate leukocyte adhesion and activation, allowing them to bind to the endothelium and migrate across it. In neutrophils, it is also a potent chemoattractant, and is able to induce the formation of reactive oxygen species and the release of lysosomal enzymes by these cells.|
|LTC4, LTD4||Eicosanoid||eosinophils, mast cells, macrophages||These three Cysteine-containing leukotrienes contract lung airways, increase micro-vascular permeability, stimulate mucus secretion, and promote eosinophil-based inflammation in the lung, skin, nose, eye, and other tissues.|
|5-oxo-eicosatetraenoic acid||Eicosanoid||leukocytes, cancer cells||Potent stimulator of neutrophil chemotaxis, lysosome enzyme release, and reactive oxygen species formation; monocyte chemotaxis; and with even greater potency eosinophil chemotaxis, lysosome enzyme release, and reactive oxygen species formation.|
|5-HETE||Eicosanoid||Leukocytes||Metabolic precursor to 5-Oxo-eicosatetraenoic acid, it is a less potent stimulator of neutrophil chemotaxis, lysosome enzyme release, and reactive oxygen species formation; monocyte chemotaxis; and eosinophil chemotaxis, lysosome enzyme release, and reactive oxygen species formation.|
|Prostaglandins||Eicosanoid||Mast cells||A group of lipids that can cause vasodilation, fever, and pain.|
|Nitric oxide||Soluble gas||Macrophages, endothelial cells, some neurons||Potent vasodilator, relaxes smooth muscle, reduces platelet aggregation, aids in leukocyte recruitment, direct antimicrobial activity in high concentrations.|
|TNF-α and IL-1||Cytokines||Primarily macrophages||Both affect a wide variety of cells to induce many similar inflammatory reactions: fever, production of cytokines, endothelial gene regulation, chemotaxis, leukocyte adherence, activation of fibroblasts. Responsible for the systemic effects of inflammation, such as loss of appetite and increased heart rate. TNF-α inhibits osteoblast differentiation.|
|Tryptase||Enzymes||Mast Cells||This serine protease is believed to be exclusively stored in mast cells and secreted, along with histamine, during mast cell activation.|
Specific patterns of acute and chronic inflammation are seen during particular situations that arise in the body, such as when inflammation occurs on an epithelial surface, or pyogenic bacteria are involved.
- Granulomatous inflammation: Characterised by the formation of granulomas, they are the result of a limited but diverse number of diseases, which include among others tuberculosis, leprosy, sarcoidosis, and syphilis.
- Fibrinous inflammation: Inflammation resulting in a large increase in vascular permeability allows fibrin to pass through the blood vessels. If an appropriate procoagulative stimulus is present, such as cancer cells, a fibrinous exudate is deposited. This is commonly seen in serous cavities, where the conversion of fibrinous exudate into a scar can occur between serous membranes, limiting their function. The deposit sometimes forms a pseudomembrane sheet. During inflammation of the intestine (Pseudomembranous colitis), pseudomembranous tubes can be formed.
- Purulent inflammation: Inflammation resulting in large amount of pus, which consists of neutrophils, dead cells, and fluid. Infection by pyogenic bacteria such as staphylococci is characteristic of this kind of inflammation. Large, localised collections of pus enclosed by surrounding tissues are called abscesses.
- Serous inflammation: Characterised by the copious effusion of non-viscous serous fluid, commonly produced by mesothelial cells of serous membranes, but may be derived from blood plasma. Skin blisters exemplify this pattern of inflammation.
- Ulcerative inflammation: Inflammation occurring near an epithelium can result in the necrotic loss of tissue from the surface, exposing lower layers. The subsequent excavation in the epithelium is known as an ulcer.
Inflammatory abnormalities are a large group of disorders that underlie a vast variety of human diseases.
Examples of disorders associated with inflammation include:
Main article: Atherosclerosis
Atherosclerosis, formerly considered a bland lipid storage disease, actually involves an ongoing inflammatory response.
Recent advances in basic science have established a fundamental role for inflammation in mediating all stages of this disease from initiation through progression and, ultimately, the thrombotic complications of atherosclerosis.
These new findings provide important links between risk factors and the mechanisms of atherogenesis.
Clinical studies have shown that this emerging biology of inflammation in atherosclerosis applies directly to human patients.
Elevation in markers of inflammation predicts outcomes of patients with acute coronary syndromes, independently of myocardial damage.
In addition, low-grade chronic inflammation, as indicated by levels of the inflammatory marker C-reactive protein, prospectively defines risk of atherosclerotic complications, thus adding to prognostic information provided by traditional risk factors.
Moreover, certain treatments that reduce coronary risk also limit inflammation.
In the case of lipid lowering with statins, this anti-inflammatory effect does not appear to correlate with reduction in low-density lipoprotein levels.
These new insights into inflammation in atherosclerosis not only increase our understanding of this disease but also have practical clinical applications in risk stratification and targeting of therapy for this scourge of growing worldwide importance.
An allergic reaction, formally known as type 1 hypersensitivity, is the result of an inappropriate immune response triggering inflammation, vasodilation, and nerve irritation.
These chemicals propagate an excessive inflammatory response characterised by blood vessel dilation, production of pro-inflammatory molecules, cytokine release, and recruitment of leukocytes.
Severe inflammatory response may mature into a systemic response known as anaphylaxis.
Inflammatory myopathies are caused by the immune system inappropriately attacking components of muscle, leading to signs of muscle inflammation.
Due to the central role of leukocytes in the development and propagation of inflammation, defects in leukocyte functionality often result in a decreased capacity for inflammatory defense with subsequent vulnerability to infection.
Dysfunctional leukocytes may be unable to correctly bind to blood vessels due to surface receptor mutations, digest bacteria (Chédiak–Higashi syndrome), or produce microbicides (chronic granulomatous disease).
In addition, diseases affecting the bone marrow may result in abnormal or few leukocytes.
Certain drugs or exogenous chemical compounds are known to affect inflammation.
Certain illicit drugs such as cocaine and ecstasy may exert some of their detrimental effects by activating transcription factors intimately involved with inflammation (e.g. NF-κB).
Inflammation orchestrates the microenvironment around tumours, contributing to proliferation, survival and migration.
On the other hand, many cells of the immune system contribute to cancer immunology, suppressing cancer.
Molecular intersection between receptors of steroid hormones, which have important effects on cellular development, and transcription factors that play key roles in inflammation, such as NF-κB, may mediate some of the most critical effects of inflammatory stimuli on cancer cells.
This capacity of a mediator of inflammation to influence the effects of steroid hormones in cells, is very likely to affect carcinogenesis on the one hand; on the other hand, due to the modular nature of many steroid hormone receptors, this interaction may offer ways to interfere with cancer progression, through targeting of a specific protein domain in a specific cell type.
Such an approach may limit side effects that are unrelated to the tumor of interest, and may help preserve vital homeostatic functions and developmental processes in the organism.
According to a review of 2009, recent data suggests that cancer-related inflammation (CRI) may lead to accumulation of random genetic alterations in cancer cells.
Role in cancer
In 1863, Rudolf Virchow hypothesized that the origin of cancer was at sites of chronic inflammation.
At present, chronic inflammation is estimated to contribute to approximately 15% to 25% of human cancers.
Mediators and DNA damage in cancer
An inflammatory mediator is a messenger that acts on blood vessels and/or cells to promote an inflammatory response.
These inflammatory mediators, and others, orchestrate an environment that fosters proliferation and survival.
Inflammation also causes DNA damages due to the induction of reactive oxygen species (ROS) by various intracellular inflammatory mediators.
ROS and RNS are normally produced by these cells to fight infection.
ROS, alone, cause more than 20 types of DNA damage.
Oxidative DNA damages cause both mutations and epigenetic alterations.
RNS also cause mutagenic DNA damages.
A normal cell may undergo carcinogenesis to become a cancer cell if it is frequently subjected to DNA damage during long periods of chronic inflammation.
In addition, mistakes in the DNA repair process may cause epigenetic alterations.
Mutations and epigenetic alterations that are replicated and provide a selective advantage during somatic cell proliferation may be carcinogenic.
Genome-wide analyses of human cancer tissues reveal that a single typical cancer cell may possess roughly 100 mutations in coding regions, 10-20 of which are “driver mutations” that contribute to cancer development.
However, chronic inflammation also causes epigenetic changes such as DNA methylations, that are often more common than mutations.
Typically, several hundreds to thousands of genes are methylated in a cancer cell (see DNA methylation in cancer).
Sites of oxidative damage in chromatin can recruit complexes that contain DNA methyltransferases (DNMTs), a histone deacetylase (SIRT1), and a histone methyltransferase (EZH2), and thus induce DNA methylation.
DNA repair genes, in particular, are frequently inactivated by methylation in various cancers (see hypermethylation of DNA repair genes in cancer).
A 2018 report evaluated the relative importance of mutations and epigenetic alterations in progression to two different types of cancer.
This report showed that epigenetic alterations were much more important than mutations in generating gastric cancers (associated with inflammation).
However, mutations and epigenetic alterations were of roughly equal importance in generating esophageal squamous cell cancers (associated with tobacco chemicals and acetaldehyde, a product of alcohol metabolism).
HIV and AIDS
It has long been recognized that infection with HIV is characterized not only by development of profound immunodeficiency but also by sustained inflammation and immune activation.
A substantial body of evidence implicates chronic inflammation as a critical driver of immune dysfunction, premature appearance of aging-related diseases, and immune deficiency.
Many now regard HIV infection not only as an evolving virus-induced immunodeficiency but also as chronic inflammatory disease.
Even after the introduction of effective antiretroviral therapy (ART) and effective suppression of viremia in HIV-infected individuals, chronic inflammation persists.
Animal studies also support the relationship between immune activation and progressive cellular immune deficiency: SIVsm infection of its natural nonhuman primate hosts, the sooty mangabey, causes high-level viral replication but limited evidence of disease.
This lack of pathogenicity is accompanied by a lack of inflammation, immune activation and cellular proliferation.
Delineating how CD4 T cells are depleted and how chronic inflammation and immune activation are induced lies at the heart of understanding HIV pathogenesis––one of the top priorities for HIV research by the Office of AIDS Research, National Institutes of Health.
These are the two signature events that propel HIV disease progression to AIDS.
Pyroptosis appears to create a pathogenic vicious cycle in which dying CD4 T cells and other immune cells (including macrophages and neutrophils) release inflammatory signals that recruit more cells into the infected lymphoid tissues to die.
The feed-forward nature of this inflammatory response produces chronic inflammation and tissue injury.
Identifying pyroptosis as the predominant mechanism that causes CD4 T-cell depletion and chronic inflammation, provides novel therapeutic opportunities, namely caspase-1 which controls the pyroptotic pathway.
In this regard, pyroptosis of CD4 T cells and secretion of pro-inflmammatory cytokines such as IL-1β and IL-18 can be blocked in HIV-infected human lymphoid tissues by addition of the caspase-1 inhibitor VX-765, which has already proven to be safe and well tolerated in phase II human clinical trials.
These findings could propel development of an entirely new class of “anti-AIDS” therapies that act by targeting the host rather than the virus.
Such agents would almost certainly be used in combination with ART.
By promoting “tolerance” of the virus instead of suppressing its replication, VX-765 or related drugs may mimic the evolutionary solutions occurring in multiple monkey hosts (e.g. the sooty mangabey) infected with species-specific lentiviruses that have led to a lack of disease, no decline in CD4 T-cell counts, and no chronic inflammation.
Resolution of inflammation
The inflammatory response must be actively terminated when no longer needed to prevent unnecessary "bystander" damage to tissues.
Failure to do so results in chronic inflammation, and cellular destruction.
Resolution of inflammation occurs by different mechanisms in different tissues.
Mechanisms that serve to terminate inflammation include:
Connection to depression
There is evidence for a link between inflammation and depression.
Inflammatory processes can be triggered by negative cognitions or their consequences, such as stress, violence, or deprivation.
Thus, negative cognitions can cause inflammation that can, in turn, lead to depression.
In addition there is increasing evidence that inflammation can cause depression because of the increase of cytokines, setting the brain into a "sickness mode".
Classical symptoms of being physically sick like lethargy show a large overlap in behaviors that characterize depression.
Levels of cytokines tend to increase sharply during the depressive episodes of people with bipolar disorder and drop off during remission.
Furthermore, it has been shown in clinical trials that anti-inflammatory medicines taken in addition to antidepressants not only significantly improves symptoms but also increases the proportion of subjects positively responding to treatment.
Inflammations that lead to serious depression could be caused by common infections such as those caused by a virus, bacteria or even parasites.
If an organism is not contained by the actions of acute inflammation it may gain access to the lymphatic system via nearby lymph vessels.
When lymph nodes cannot destroy all pathogens, the infection spreads further.
A pathogen can gain access to the bloodstream through lymphatic drainage into the circulatory system.
When inflammation overwhelms the host, systemic inflammatory response syndrome is diagnosed.
Inflammation also induces high systemic levels of acute-phase proteins.
In acute inflammation, these proteins prove beneficial; however, in chronic inflammation they can contribute to amyloidosis.
Inflammation often affects the numbers of leukocytes present in the body:
- Leukocytosis is often seen during inflammation induced by infection, where it results in a large increase in the amount of leukocytes in the blood, especially immature cells. Leukocyte numbers usually increase to between 15 000 and 20 000 cells per microliter, but extreme cases can see it approach 100 000 cells per microliter. Bacterial infection usually results in an increase of neutrophils, creating neutrophilia, whereas diseases such as asthma, hay fever, and parasite infestation result in an increase in eosinophils, creating eosinophilia.
- Leukopenia can be induced by certain infections and diseases, including viral infection, Rickettsia infection, some protozoa, tuberculosis, and some cancers.
Systemic inflammation and obesity
Although the processes involved are identical to tissue inflammation, systemic inflammation is not confined to a particular tissue but involves the endothelium and other organ systems.
Chronic inflammation is widely observed in obesity.
Obese people commonly have many elevated markers of inflammation, including:
Low-grade chronic inflammation is characterized by a two- to threefold increase in the systemic concentrations of cytokines such as TNF-α, IL-6, and CRP.
Waist circumference correlates significantly with systemic inflammatory response.
Loss of white adipose tissue reduces levels of inflammation markers.
The association of systemic inflammation with insulin resistance and type 2 diabetes, and with atherosclerosis is under preliminary research, although rigorous clinical trials have not been conducted to confirm such relationships.
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.
Here are the possible outcomes to inflammation:
- Resolution The complete restoration of the inflamed tissue back to a normal status. Inflammatory measures such as vasodilation, chemical production, and leukocyte infiltration cease, and damaged parenchymal cells regenerate. In situations where limited or short-lived inflammation has occurred this is usually the outcome.
- Fibrosis Large amounts of tissue destruction, or damage in tissues unable to regenerate, cannot be regenerated completely by the body. Fibrous scarring occurs in these areas of damage, forming a scar composed primarily of collagen. The scar will not contain any specialized structures, such as parenchymal cells, hence functional impairment may occur.
- Abscess formation A cavity is formed containing pus, an opaque liquid containing dead white blood cells and bacteria with general debris from destroyed cells.
- Chronic inflammation In acute inflammation, if the injurious agent persists then 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 the dominating presence of macrophages in the injured tissue. 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. As a consequence, chronic inflammation is almost always accompanied by tissue destruction.
Inflammation is usually indicated by adding the suffix "", as shown below.
More examples are available at list of types of inflammation.
Credits to the contents of this page go to the authors of the corresponding Wikipedia page: en.wikipedia.org/wiki/Inflammation.