What is inflammation?
In response to tissue injury or foreign invaders, our immune system raises some uncomfortable responses called inflammation.
These uncomfortable responses by immune system is necessary to bring the immune cells to the site of infection rapidly and in huge numbers so that they can resolve the issue and return the infected tissue in its healthy and functional state. So short-term inflammation is actually good and essential to fight an infection or to promote healing process. The problem arises when the inflammation goes on for a long period of time. This is called long-term or chronic inflammation which may last for months, or years without any defined symptoms and even when the underlying cause is resolved.
Acute inflammation
Acute inflammation is an immediate response of innate immunity due to injury or infection, which lasts for few hours to days. The symptoms of acute inflammation usually resolve within three days. The causes of acute inflammation are-
-Injury
-Infection
-Exposure to sun, chemicals, dust, and some other substances (constant exposure to these substances may also lead to chronic inflammation).
Chronic inflammation
If acute inflammation fails to address the infection or healing process and persists for a long time, we call it chronic inflammation. It’s an ongoing response, may last for months to years. Frequent occurrence of acute inflammation may also progress to chronic stages. However, in certain conditions, chronic inflammation may occur independently of acute inflammation. For example, Mycobacterium Tuberculosis (that causes tuberculosis) infection could resist host defenses and stay in the body for a long time. Chronic inflammation is a “silent killer” that affects tissues, organs, joints, and blood vessels. Since it does not show any reliable signs or symptoms, you may not notice until it causes significant damage to your body.
Effects of inflammation
The classical signs/symptoms of acute inflammation are heat, pain, redness, swelling, and loss of function (e.g. sensing smell, joint mobility). The activation of white blood cells and the substance they release causes increase in blood flow through the vessels, so the skin becomes red and warm. Some of the released chemical substances, such as histamine, bradykinin, and prostaglandin cause dilation of the blood vessel so the blood fluid leaks into the surrounding tissue, leading to tissue swelling. This process may activate nerve pathway, resulting in pain.
The beneficial effects of acute inflammation include – dilution of toxins, inflammatory cell infiltration into the site of infection, entry of serum antibodies, drug transport, oxygen and nutrients transport, and killing or inactivating pathogens. The detrimental effect of acute inflammation is normal tissue destruction.
However, in chronic inflammation, the signs are not so obvious and depends on the associated disease conditions. Chronic response may include above mentioned signs but may vary in their severity and duration. During chronic inflammation, macrophages may incite various effects that causes progressive tissue damage and subsequent functional impairment.
What triggers chronic inflammation?
Obesity
Obesity is a characteristic feature of metabolic syndrome (refers to a cluster of risk factors including high insulin, high blood sugar, excessive fat around waist, high LDL (bad cholesterol) and low HDL (good cholesterol) that increases the risk of developing cardiovascular disease, heart disease, stroke, and diabetes) which is highly correlated with chronic inflammation in obese people. The excessive macronutrients in the fat depots lowers protective adiponectin, whereas triggers pro-inflammatory cytokines, such as TNFa and IL6 release. The increased levels of IL6 causes liver to produce more C-reactive protein (CRP), a marker of chronic inflammation. Therefore, loosing extra pounds especially belly fat helps lower your risk of chronic inflammation significantly.
Stress
Psychological stress stimulates inflammatory response. Glucocorticoids, one of the leading stress hormones have been evidenced to significantly increase pro-inflammatory* response. While some other research suggests its protective effects. So why this contradictory results? The answer is probably linked to the duration of stress. It is observed that acute stressors (lasting only minutes, such as exams) helps to regulate healthy immune function by preserving adaptive immunity, whereas chronic stressors disrupt the balance between pro- and anti-inflammatory response.
Autoimmune disorders
An autoimmune condition arises when our immune system mistakenly attacks our own body. In this case, the immune system cannot differentiate between foreign pathogens from body’s own healthy cells, leading to tissue damage or organ failure.
autoimmune reactions trigger chronic inflammatory diseases, including inflammatory bowel disease (IBD), rheumatoid arthritis (RA), gout, systemic lupus erythematosus, and diabetes.
Hidden infection
Chronic inflammation can be a result of hidden infection with bacteria, virus, yeasts, or parasites. A good example of latent infection is probably by Herpes Simplex virus 1 (oral herpes that causes fever blister or cold sores) that affects 67% of the population worldwide under the age of 50, according to World Health Organization. There is no cure for this infection. Once this virus gets into your systems it will be there for forever and may show frequent outbreaks. Antiviral drugs can lower the severity and frequency of outbreaks. Moreover, this hidden infection is often an underlying cause of autoimmune disease that stimulates chronic inflammation.
Persistent acute inflammation
The presence of non-degradable substances, foreign bodies, latent pathogens like Herpes virus, as well as autoimmune reactions may trigger persistent acute inflammation, and subsequently chronic disorders.
Granulomatous inflammation
Granulomatous inflammation is a type of chronic inflammation. It consists of a set of mature macrophages that are organized to form multinucleated foreign body giant cells. Giant cells form when the pathogens or foreign bodies are large enough for a single macrophage (the size of a single macrophage is 25-50 microns) to engulf. Thus, 10s to 100s of macrophages fuse together that can engulf particles with a size of few hundred microns. The giant cells can persist for a decade in the reaction site. Foreign body granulomatous reaction is typically observed during M. Tuberculosis infection. It may also be invoked by industrial dust, such as silica, asbestos, talc, and inhaled cotton fibers in textile industry. Some metals, polymers, as well as wear debris from implanted biomaterials may also cause this type of reaction.
Foreign substances
Some foreign substances may not be removed by phagocytosis or enzymatic degradation, such as inhaling silica dust, long term exposure to an irritant (industrial chemicals) or objects that gain entry into the body like wood or metal splinters.
Allergens
It can be non-infectious substances from environment that stimulates immunoglobulin E (IgE) production, thus ‘sensitizing’ the subject and induces allergic reaction upon exposure to that substance again in later. This group includes grass & pollens, sheddings from skin and fur, dust particles, some foods (like tree nuts, peanuts, dairy, eggs), latex, certain medicines, implant biomaterials, and insect venoms. The exposure to these allergens may induce immediate early-phase or acute hypersensitivity reactions. However, repetitive, or persistent exposure to allergens may cause local recruitment and activation of leukocytes, that promotes chronic inflammation.
Gluten- & lectin-rich foods
Lectin is known as a ‘carbohydrate binding protein’ found in most plants, and particularly in legumes, seeds, and grains (e.g., wheat, barley, quinoa, and rice). Gluten consists of a complex protein network commonly found in wheat, rye, barley, oats, and triticale. The two main protein components of gluten are – gliadin, and glutenin of which gliadin is proven to incite adverse immune response in celiac disease (an autoimmune condition) due to its proline-rich tight compact network and which makes it undigestible by gastric, pancreatic, as well as intestinal proteolytic enzymes in the gastrointestinal tract. Both gluten and lectin can interact with the small intestinal linings, increase gut permeability, and then pass through the gut barriers to enter the blood stream via local lymph nodes. This leaky gut syndrome is an alarming signal for chronic inflammation or autoimmune diseases.
Although, pressure cooking can remove most of the lectin, gluten is heat resistant and thereby life-long gluten-free diet or its minimal consumption is prescribed for people with certain immune conditions, such as celiac disease, irritable bowel syndrome, gluten ataxia, gluten sensitivity, and wheat allergy (allergic reactions to any of the four types of wheat protein- gluten, gliadin, globulin, and albumin).
Smoking
Cigarette smoke comprises thousands of chemicals that are produced during the burning of tobacco. The immunomodulatory toxins in cigarette are – nicotine, carbon monoxide, acrolein, reactive oxidant substances (ROS), and many more. These constituents, particularly ROS, activates intracellular signaling cascades of epithelial cells lining the airways, leading to inflammatory gene activation (such as TNFa, interleukin 8), and resulting in chronic recruitment of immune cells and inflammation.
Sedentary lifestyle
Sedentary behavior is highly correlated with adiposity-related inflammation. Physical inactivity promotes obesity, especially belly fat (or visceral fat cushioning the internal organs of the body) accumulation that is highly associated with metabolic syndrome and chronic inflammation. In a study, reducing sedentary time in women with newly diagnosed type 2 diabetes reduced CRP levels and IL6.
Aging
In older individuals, elevated levels of pro-inflammatory markers are often observed in circulating blood and other tissues, a phenomenon called inflammageing. Inflammageing is a significant risk factor for cardiovascular diseases, multimorbidity, physical and cognitive disability, and premature death.
During ageing, accumulation of visceral fat produces pro-inflammatory cytokines that causes massive infiltration of macrophages, lymphocytes, and senescent cells (senescent cells do not divide and possess distinctive phenotypic and secretory behaviors) that furthers inflammageing. The other potential underlying causes of inflammageing include – genomic instability, cell senescence, mitochondrial dysfunction, changes in microbiota composition, increase in gut permeability, impaired autophagy (leads to impaired recycling or removal of cellular debris), oxidative stress, activation of NLRP3 inflammasome, immune cell dysregulation, and chronic infections. Moreover, dysregulated, or unresolved local tissue inflammation can progress to chronic systemic inflammation during ageing.
Diseases associated with chronic inflammation
Allergies, diabetes, cardiovascular disease, arthritis, rheumatoid arthritis (RA), psoriasis, chronic obstructive pulmonary disease (COPD), asthma, sinusitis, peptic ulcer, ulcerative colitis, crohn’s disease, periodontitis, active hepatitis, tuberculosis, hay fever, cardiovascular disease, hypertension, atherosclerosis, aortic aneurysms, some cancers, depression, and neurodegenerative diseases like Alzheimer’s disease.
Diagnosing inflammation
Blood markers include- Ferritin, C-reactive protein (CRP), CPK, TNFa, IL6, and homocysteine.
Managing inflammation
Healthy lifestyle and balanced diet are the best way to manage chronic inflammation
1. Avoid pro-inflammatory foods and embrace anti-inflammatory diet
2. Antioxidants and mineral supplements can fight inflammation
3. Exercise regularly or increase physical activity.
4. Manage stress
5. Maintain personal hygiene
*Pro-inflammatory- Make disease worse
*Anti-inflammatory- Promote healing
References
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