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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. The classical signs of inflammation are heat, pain, redness, swelling, and loss of function. Inflammation is a generic response, and therefore it is considered as a mechanism of innate immunity, as compared to adaptive immunity, which is specific for each pathogen. Too little inflammation could lead to progressive tissue destruction by the harmful stimulus (e.g. bacteria) and compromise the survival of the organism. In contrast, chronic inflammation may lead to a host of diseases, such as hay fever, periodontitis, atherosclerosis, rheumatoid arthritis, and even cancer (e.g., gallbladder carcinoma). Inflammation is therefore normally closely regulated by the body. 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. A series of biochemical events propagates and matures the inflammatory response, involving the local vascular system, the immune system, and various cells within 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 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 as there are many pathological situations where inflammation is not driven by microbial invasion – for example, atherosclerosis, type III hypersensitivity, trauma, ischaemia. There are also pathological situations where microbial invasion does not result in classic inflammatory response—for example, parasitosis, eosinophilia.


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.


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. In sharp contrast, experimental SIVsm infection of rhesus macaque produces immune activation and AIDS-like disease with many parallels to human HIV infection. 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. Recent studies demonstrated that caspase-1-mediated pyroptosis, a highly inflammatory form of programmed cell death, drives CD4 T-cell depletion and inflammation by HIV. 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: |30px|30px|Charles Serhan}}

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. name="Cox et al. (2012)">{{cite journal |last1= Cox |first1=William T. L. |last2= Abramson |first2= Lyn Y. |last3= Devine |first3= Patricia G. |last4= Hollon |first4= Steven D. |year= 2012 |title= Stereotypes, Prejudice, and Depression: The Integrated Perspective |journal= Perspectives on Psychological Science |volume= 7 |issue= 5 |pages= 427–449 |publisher= |doi= 10.1177/1745691612455204 |pmid=26168502}} 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 depressive episodes in manics 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.

Systemic effects

An infectious organism can escape the confines of the immediate tissue via the circulatory system or lymphatic system, where it may spread to other parts of the body. If an organism is not contained by the actions of acute inflammation it may gain access to the lymphatic system via nearby lymph vessels. An infection of the lymph vessels is known as lymphangitis, and infection of a lymph node is known as lymphadenitis. 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. When it is due to infection, the term sepsis is applied, with the terms bacteremia being applied specifically for bacterial sepsis and viremia specifically to viral sepsis. Vasodilation and organ dysfunction are serious problems associated with widespread infection that may lead to septic shock and death.

Acute-phase proteins

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. These proteins include C-reactive protein, serum amyloid A, and serum amyloid P, which cause a range of systemic effects including:

Leukocyte numbers

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

With the discovery of interleukins (IL), the concept of systemic inflammation developed. 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. The obese 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. A predominant factor in this correlation is due to the autoimmune response triggered by adiposity, whereby immune cells may mistake fatty deposits for intruders. The body attacks fat similar to bacteria and fungi. When expanded fat cells leak or break open, macrophages mobilize to clean up and embed into the adipose tissue. Then macrophages release inflammatory chemicals, including TNF-α and IL-6. TNF's primary role is to regulate the immune cells and induce inflammation. White blood cells then assist by releasing more cytokines. This link between adiposity and inflammation has been shown to produce 10–35% of IL-6 in a resting individual, and this production increases with increasing adiposity. Loss of white adipose tissue reduces levels of inflammation markers. The association of systemic inflammation with insulin resistance and atherosclerosis is the subject of intense research. In the obese mouse models, inflammation and macrophage-specific genes are upregulated in white adipose tissue (WAT). There were also signs of dramatic increase in circulating insulin level, adipocyte lipolysis and formation of multinucleate giant cells. The fat-derived protein called angiopoietin-like protein 2 (Angptl2) elevates in fat tissues. Higher than normal Angptl2 level in fat tissues develop inflammation as well as insulin and leptin resistance. Stored fat secretes Leptin to signal satiety. Leptin resistance plays a role in the process where appetite overrules the message of satiety. Angptl2 then starts an inflammatory cascade causing blood vessels to remodel and attract macrophages. Angptl2 is an adipocyte-derived inflammatory mediator linking obesity to systemic insulin resistance. It is possible that, as an inflammatory marker, leptin responds specifically to adipose-derived inflammatory cytokines. C-reactive protein (CRP) is generated at a higher level in obese people. It raises when there is inflammation throughout the body. Mild elevation in CRP increase risk of heart attacks, strokes, high blood pressure, muscle weakness and fragility.

Systemic inflammation and overeating

Hyperglycemia induces IL-6 production from endothelial cells and macrophages. Meals high in saturated fat, as well as meals high in calories have been associated with increases in inflammatory markers. In addition, interstitial abdominal adiposity (also referred to as accumulated intra-abdominal fat) may be a factor in increasing systemic risk for multiple inflammatory diseases. Although the exact mechanisms are still being investigated, a review published in 2010 suggested that significant growth of adipose tissue in response to overeating can evoke a chronic inflammatory response.


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:
  1. ResolutionThe 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.
  2. FibrosisLarge 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.
  3. Abscess formationA cavity is formed containing pus, an opaque liquid containing dead white blood cells and bacteria with general debris from destroyed cells.
  4. Chronic inflammationIn 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. However, some conditions such as asthma and pneumonia do not follow this convention. More examples are available at list of types of inflammation. File:Acute_Appendicitis.jpg|Acute appendicitis File:Dermatitis.jpg|Acute dermatitis File:Streptococcus pneumoniae meningitis, gross pathology 33 lores.jpg|Acute infective meningitis File:Tonsillitis.jpg|Acute tonsillitis

Diet and inflammation

The Dietary Inflammatory Index (DII) is a score (number) that describes the potential of diet to modulate systemic inflammation within the body. As stated chronic inflammation is linked to most chronic diseases including arthritis, many types of cancer, cardiovascular diseases, inflammatory bowel diseases, and diabetes.

Exercise and inflammation

Exercise-induced acute inflammation

Acute inflammation of the muscle cells, as understood in exercise physiology, can result after induced eccentric and concentric muscle training. Participation in eccentric training and conditioning, including resistance training and activities that emphasize eccentric lengthening of the muscle including downhill running on a moderate to high incline can result in considerable soreness within 24 to 48 hours, even though blood lactate levels, previously thought to cause muscle soreness, were much higher with level running. This delayed onset muscle soreness (DOMS) results from structural damage to the contractile filaments and z-disks, which has been noted especially in marathon runners whose muscle fibers revealed remarkable damage to the muscle fibers after both training and marathon competition . The onset and timing of this gradient damage to the muscle parallels the degree of muscle soreness experienced by the runners. Z-disks are the point of contact for the contractile proteins. They provide structural support for transmission of force when muscle fibers are activated to shorten. However, in marathon runners and those who subscribe to the overload principle to enhance their muscles, show moderate Z-disk streaming and major disruption of thick and thin filaments in parallel groups of sarcomeres as a result of the force of eccentric actions or stretching of tightened muscle fibers. This disruption of muscle fibers triggers white blood cells to increase following induced muscle soreness, leading to the inflammatory response observation from induced muscle soreness. Elevations in plasma enzymes, myoglobinemia, and abnormal muscle histology and ultrastructure are concluded to be associated with inflammatory response. High tension in the contractile-elastic system of muscle results in structural damage to the muscle fiber and plasmalemma and its epimysium, perimysium, and/or endomysium. The mysium damage disrupts calcium homeostasis in injured fibers and fiber bundles, resulting in necrosis that peaks about 48 hours after exercise. The products of macrophage activity and intracellular contents (such as histamines, kinins, and K+) accumulate outside cells. These substances then stimulate free nerve endings in the muscle; a process that appears accentuated by eccentric exercise, in which large forces are distributed over a relatively small cross-sectional area of the muscle .

Post-inflammatory muscle growth and repair

There is a known relationship between inflammation and muscle growth. For instance, high doses of anti-inflammatory medicines (e.g., NSAIDs) are able to blunt muscle growth. Cold therapy has been shown to negatively affect muscle growth as well. Reducing inflammation results in decreased macrophage activity and lower levels of IGF-1 Acute effects of cold therapy on training adaptations show reduced satellite cell proliferation. Long term effects include less muscular hypertrophy and an altered cell structure of muscle fibers. It has been further theorized that the acute localized inflammatory responses to muscular contraction during exercise, as described above, are a necessary precursor to muscle growth. As a response to muscular contractions, the acute inflammatory response initiates the breakdown and removal of damaged muscle tissue. Muscles can synthesize cytokines in response to contractions, such that the cytokines interleukin-1 beta (IL-1β), TNF-α, and IL-6 are expressed in skeletal muscle up to 5 days after exercise. In particular, the increase in levels of IL-6 ( interleukin 6), a myokine, can reach up to one hundred times that of resting levels. Depending on volume, intensity, and other training factors, the IL-6 increase associated with training initiates about 4 hours after resistance training and remains elevated for up to 24 hours. These acute increases in cytokines, as a response to muscle contractions, help initiate the process of muscle repair and growth by activating satellite cells within the inflamed muscle. Satellite cells are crucial for skeletal muscle adaptation to exercise. They contribute to hypertrophy by providing new myonuclei and repair damaged segments of mature myofibers for successful regeneration following injury- or exercise-induced muscle damage; high-level powerlifters can have up to 100% more satellite cells than untrained controls. A rapid and transient localization of the IL-6 receptor and increased IL-6 expression occurs in satellite cells following contractions. IL-6 has been shown to mediate hypertrophic muscle growth both in vitro and in vivo. Unaccustomed exercise can increase IL-6 by up to sixfold at 5 hours post-exercise and threefold 8 days after exercise. Also telling is the fact that NSAIDs can decrease satellite cell response to exercise, thereby reducing exercise-induced protein synthesis. The increase in cytokines ( myokines) after resistance exercise coincides with the decrease in levels of myostatin, a protein that inhibits muscle differentiation and growth. The cytokine response to resistance exercise and moderate-intensity running occur differently, with the latter causing a more prolonged response, especially at the 12–24 hour mark. Developing research has demonstrated that many of the benefits of exercise are mediated through the role of skeletal muscle as an endocrine organ. That is, contracting muscles release multiple substances known as myokines, including but not limited to those cited in the above description, which promote the growth of new tissue, tissue repair, and various anti-inflammatory functions, which in turn reduce the risk of developing various inflammatory diseases. The new view that muscle is an endocrine organ is transforming our understanding of exercise physiology and with it, of the role of inflammation in adaptation to stress.

Chronic inflammation and muscle loss

Both chronic and extreme inflammation are associated with disruptions of anabolic signals initiating muscle growth. Chronic inflammation has been implicated as part of the cause of the muscle loss that occurs with aging. Increased protein levels of myostatin have been described in patients with diseases characterized by chronic low-grade inflammation. Increased levels of TNF-α can suppress the AKT/mTOR pathway, a crucial pathway for regulating skeletal muscle hypertrophy,Shih, Michael. "Skeletal Muscle Hypertrophy Is Regulated via AKT/mTOR Pathway." BioCarta. Web. 21 March 2011. thereby increasing muscle catabolism. Cytokines may antagonize the anabolic effects of insulin-like growth factor 1 (IGF-1). In the case of sepsis, an extreme whole body inflammatory state, the synthesis of both myofibrillar and sarcoplasmic proteins are inhibited, with the inhibition taking place preferentially in fast-twitch muscle fibers. Sepsis is also able to prevent leucine from stimulating muscle protein synthesis. In animal models, when inflammation is created, mTOR loses its ability to be stimulated by muscle growth.

Exercise as a treatment for inflammation

Regular physical activity is reported to decrease markers of inflammation, although the correlation is imperfect and seems to reveal differing results contingent upon training intensity. For instance, while baseline measurements of circulating inflammatory markers do not seem to differ greatly between healthy trained and untrained adults, long-term training may help reduce chronic low-grade inflammation. On the other hand, levels of the anti-inflammatory myokine IL-6 ( interleukin 6) remained elevated longer into the recovery period following an acute bout of exercise in patients with inflammatory diseases, relative to the recovery of healthy controls. It may well be that low-intensity training can reduce resting pro-inflammatory markers (CRP, IL-6), while moderate-intensity training has milder and less-established anti-inflammatory benefits. There is a strong relationship between exhaustive exercise and chronic low-grade inflammation. Marathon running may enhance IL-6 levels as much as 100 times over normal and increases total leuckocyte count and neturophil mobilization. Regarding the above, IL-6 had previously been classified as a proinflammatory cytokine. Therefore, it was first thought that the exercise-induced IL-6 response was related to muscle damage. However, it has become evident that eccentric exercise is not associated with a larger increase in plasma IL-6 than exercise involving concentric “nondamaging” muscle contractions. This finding clearly demonstrates that muscle damage is not required to provoke an increase in plasma IL-6 during exercise. As a matter of fact, eccentric exercise may result in a delayed peak and a much slower decrease of plasma IL-6 during recovery. Recent work has shown that both upstream and downstream signalling pathways for IL-6 differ markedly between myocytes and macrophages. It appears that unlike IL-6 signalling in macrophages, which is dependent upon activation of the NFκB signalling pathway, intramuscular IL-6 expression is regulated by a network of signalling cascades, including the Ca2+/NFAT and glycogen/p38 MAPK pathways. Thus, when IL-6 is signalling in monocytes or macrophages, it creates a pro-inflammatory response, whereas IL-6 activation and signalling in muscle is totally independent of a preceding TNF-response or NFκB activation, and is anti-inflammatory. Several studies show that markers of inflammation are reduced following longer-term behavioural changes involving both reduced energy intake and a regular program of increased physical activity, and that, in particular, IL-6 was miscast as an inflammatory marker. For example, the anti-inflammatory effects of IL-6 have been demonstrated by IL-6 stimulating the production of the classical anti-inflammatory cytokines IL-1ra and IL-10. As such, individuals pursuing exercise as a means to treat the causal factors underlying chronic inflammation are pursuing a course of action strongly supported by current research, as an inactive lifestyle is strongly associated with the development and progression of multiple inflammatory diseases. Note that cautions regarding over-exertion may apply in certain cases, as discussed above, though this concern rarely applies to the general population.

Signal-to-noise theory

Given that localized acute inflammation is a necessary component for muscle growth, and that chronic low-grade inflammation is associated with a disruption of anabolic signals initiating muscle growth, it has been theorized that a signal-to-noise model may best describe the relationship between inflammation and muscle growth.Pilon, Brad. " Inflammation Affects Your Ability to Build Muscle" Inflammation Theory By keeping the "noise" of chronic inflammation to a minimum, the localized acute inflammatory response signals a stronger anabolic response than could be achieved with higher levels of chronic inflammation.

See also


External links

"green air" © 2007 - Ingo Malchow, Webdesign Neustrelitz
This article based upon the http://en.wikipedia.org/wiki/Inflammation, the free encyclopaedia Wikipedia and is licensed under the GNU Free Documentation License.
Further informations available on the list of authors and history: http://en.wikipedia.org/w/index.php?title=Inflammation&action=history
presented by: Ingo Malchow, Mirower Bogen 22, 17235 Neustrelitz, Germany