Infectious and non-infectious causes of chronic inflammation

In this article, I briefly explain the infectious and non-infectious causes of chronic inflammation.

Chronic inflammation

Chronic inflammation is a slow and long-running inflammation that can last for many months to years. It varies with its extent and effects relating to the cause of the injury and the resilience of the body towards the inflammation.

Autoimmune disorders are the most common causes of chronic inflammation. Apart from this, exposure to toxicity or untreated acute inflammation are some of the other causes of chronic inflammation.

Innate immune cells release inflammatory mediators, which cause widespread immune response resulting in symptoms of muscle aches and fever. In the majority of cases, the clearance of antigens, allergens, or toxins helps in relieving distress.

However, in certain cases, an inflammatory tendency continues, which gradually generates a chronic inflammatory response with systemic effects. Chronic inflammation is identified with a persistent and elevated expression of inflammatory cytokines.

Infections- The cause of chronic inflammation

Chronic inflammation can be a cause of an infection, where a pathogen easily and continuously accesses the body. A body can be unprotected from continuous entry of microbes and stimulation of immunity as a result of gum disease and unhealed wounds. Gut microbes also contribute to chronic inflammatory bowel disease.

Commensal bacteria present in our gut play a vital role in lessening the reactions caused by ingesting microbes. However, due to the antibiotics we take to combat infections do have a disrupting effect on gut microbes, and as a result, gut microbes become contributors to chronic inflammation.

Harmful pathogens eluding the immune system cause chronic inflammation and stay in the body for a long time. Pathogens like mycobacteria and fungi often elude our immune system and relentlessly stimulate our immune cells that release inflammatory cytokines and other mediators.

Pathogens: Not the only cause of chronic inflammation

Several other factors, along with pathogens, are responsible for chronic inflammation. When tissue gets physically damaged, it releases damage-associated molecular patterns (DAMPs), which are responsible for inducing the secretion of inflammatory cytokines and other mediators as innate immune responses.

If the tissue damage does not heal, the inflammatory stimulus continues to secrete cytokines and mediators. Many diseases like Alzheimer’s, atherosclerosis, tumors, and autoimmune disorders result in tissue damage and stimulate innate and adaptive responses. They are the non-infectious causes of chronic inflammation. Other than these, obesity is also one of the most common causes of chronic inflammation.

Obesity is linked with a cluster of metabolic and systemic disorders. According to some recent research studies, inflammation mediates many of the systemic effects of obesity.

Our immune system is not the only producer of inflammatory cytokines, which are also produced by visceral adipocytes. Visceral adipocytes are fat cells that are quite responsive and hyperactive. They generate metabolism-regulatory hormones along with various proinflammatory mediators such as TNF-α and IL-6.

The cause behind the release of hormones and mediators is believed to be related to stress factors. Excessive lipid buildup is related to intracellular stress, which spurs signals to produce cytokines and inflammatory mediators.

A common result of obesity, free fatty acids can bind toll-like receptors on adipocytes, thus initiating a signal cascade. This signal cascade is comparable to the cascade induced by a pathogen, producing inflammatory cytokines.

However, around 6% of obese individuals do not produce inflammatory cytokines but show some signs of metabolic dysfunction. These obese individuals can tolerate excess fats may be due to genetic disparities.

Systemic disease may be a consequence of chronic inflammation

The effects of chronic inflammation vary from person to person depending on the age, sex, and health condition, along with the tissue of origin. Individuals suffering from chronic inflammation have an elevated circulation of inflammatory mediators, including IL-6, IL-1, and TNF-α, and many undergo systemic disorders.

The most common consequence of chronic inflammation- Type 2 diabetes

The failure of insulin signaling in a person leads to general metabolic dysfunction and causes diabetes. Pancreatic islet cells produce insulin and due to autoimmunity, these cells undergo destruction, which results in type-1 diabetes. However, when cells fail to respond to insulin, they develop a condition called insulin resistance, which impedes in proper regulation of glucose levels and ultimately leads to type-2 diabetes.

Some signaling cascades, induced by cytokines TNF-α and IL-6, interfere with the ability of the insulin receptor, thus hindering the activation of required downstream events. Stress and inflammatory responses lead to activation of JNK (c-Jun N-terminal) and MAPK (mitogen-activated protein kinase) signaling pathways. A key downstream mediator of insulin receptor signaling, IRS-1 is phosphorylated and inactivated by JNK.

Visceral adipocytes, in response to excessive lipid release inflammatory cytokines, induce signals that impede insulin signaling. Inhibition of insulin signaling leads to insulin resistance, the main reason for type-2 diabetes.

It was discovered around a hundred years ago that patients receiving aspirin or salicylate for inflammation or pain showed an elevated sensitivity to insulin. Studies also demonstrated that patients suffering from infectious diseases like hepatitis C, and HIV and autoimmune diseases like rheumatoid arthritis showed resistance to insulin. The insulin resistance was treated and improved with anti-inflammatory drugs.

Chronic inflammation increases vulnerability to other diseases

Inflammatory cytokines help to increase blood vessel flow and blood vessel formation in the process of healing, which also includes activation of fibroblasts and immune cells.

Inflammatory cytokines, also as part of the healing process, regulate the death of infected or damaged cells. All these things help the immune system to find pathogens easily.

If the healing process is continuously stimulated, then it has reverse consequences. Fibroblasts, when excessively stimulated, cause fibrosis or scarring of tissue, which may lead to impaired organ function.

Mutations may arise as a result of incessant stimulation of cell proliferation, which can cause the formation of tumors. Cells can survive in solid tumors as a result of the enhancement of the formation of blood vessels.

Chronic and acute inflammation can be distinguished by considering the accumulation of granulocytes and agranulocytes at the site of inflammation.

In acute inflammation, accumulation of neutrophils takes place, whereas in chronic inflammation, monocytes, macrophages, and lymphocytes accumulate at the inflammation site.

Some genes associate to encode proteins that are involved in innate and inflammatory responses with inflammatory diseases like inflammatory bowel diseases and autoinflammatory diseases. This signifies the contribution of genetics to inflammatory responses.

Conclusion

Chronic inflammation mostly happens due to autoimmune disorders. Exposure to toxicity or untreated acute inflammation are some of the other causes of chronic inflammation. Chronic inflammation is identified with a persistent and elevated expression of inflammatory cytokines. There are involvement of both infectious and non-infectious causes of chronic inflammation.

when a pathogen easily and continuously accesses the body, it leads to infection, which causes chronic inflammation. Pathogens like mycobacteria and fungi often elude our immune system and incessantly stimulate our immune cells that release inflammatory cytokines and other mediators.

Type-2 diabetes is a consequence of chronic inflammation. When cells fail to respond to insulin, they develop a condition called insulin resistance, which impedes in proper regulation of glucose levels and ultimately leads to type-2 diabetes.

The continuous stimulation of the healing process increases vulnerability to other diseases.

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