What Is Metabolic Inflammation?
The downside of inflammation is the collateral damage to the tissue. Anti-inflammatory cytokines and chemokines are responsible for suppressing pro-inflammatory cytokines and chemokines. If, somehow, there is imbalance between the two, then it leads to exaggerated inflammatory response, which in turn causes more collateral damage and pathology to the host tissue. Exaggerated inflammatory response in the body could lead to tissue damage and non-resolving inflammation that might lead to malfunction of the tissue chronically. This chronic malfunction of the tissues as a result of inflammation leading to metabolic disease is termed as metabolic inflammation.1
What Are The Metabolic Diseases Associated With Inflammation?
Metabolic inflammation can lead to hoard of diseases, namely, diabetes mellitus, Cardiovascular diseases, Alzheimer’s disease, Parkinson’s disease, cancer, infertility, PCOD, fatty liver disease, gout, hypertension, chronic kidney disease, macular degeneration, heart arrhythmias, cardiomyopathy, increased blood clotting, autoimmune disorder, arthritis, chronic depression, PTSD, heart valve failure, cataracts, schizophrenia, fibromyalgia, bipolar disorder, neuropathy, alopecia, chronic concussion effects and poor tissue repair.2
In obesity, the levels of pro-inflammatory cytokines (TNF-alpha, IL-6 and CRP) are elevated, which leads to chronic low grade inflammation. Due to hypoxia, there is an increase in necrosis along with macrophage infiltration in the adipose tissue that leads to overproduction of pro-inflammatory chemokines resulting in localized inflammation in adipose tissue and ultimately disseminated systemic inflammation that leads to other obesity-associated comorbidities.3
Diabetes mellitus is associated with increased levels of blood glucose secondary to peripheral insulin resistance and/or decreased production of insulin by pancreas. Insulin sensitivity is also linked with inflammation with studies indicating increased levels of pro-inflammatory cytokines in individuals with obesity and diabetes. Insulin secretion from the pancreatic beta cells is impaired due to chronically elevated free fatty acids and glucose levels in blood leading to type 2 diabetes mellitus. IL-1B plays a crucial role in the impairment of pancreatic beta cells and its function.4
Gout is another metabolic disease characterized by increased concentration of uric acid crystals in the joints leading to inflammatory pain and swelling of various joints.
Atherosclerosis is a cardiovascular disease in which atherosclerotic plaques accumulate in the cardiac blood vessels. It is correlated with hyperlipidemia (increased lipid levels in blood) due to obesity. Increased levels of IL-1B and IL-18 have been shown to increase the severity of atherosclerosis. The differentiation of monocytes to macrophages and then to foam cells plays a vital role in the disease progression as foam cells are pathognomonic of atherosclerotic plaques.5
Non-alcoholic fatty liver disease is another disease characterized by progression to chronic liver inflammation leading to other liver conditions including liver cirrhosis, portal hypertension and hepatocellular carcinoma. It is largely associated with obesity and hyperlipidemia.
Inflammation is the body’s immune response to any foreign body (virus, fungi, and bacteria), trauma or any kind of injury with the cardinal signs of rubor (redness), tumor (swelling), calor (increased temperature), dolor (pain) and functio laesa (loss of function). We, often, presume inflammation as an undesirable response, but it is an advantageous process that helps in the destruction or isolation of the cause of disturbance in the body as well as damage minimization and removal of damaged tissues as well as restoration of tissue homeostasis.
How Does Inflammation Take Place?
Cytokines are the most important immunomodulatory constituent of the immune system that plays the vital role in inflammation. The inflammatory cascade starts with the identification of damage or infection. The next step is the activation of nuclear factor kappa- B (NF-kB) by trans membrane toll-like receptors (TLRs). Following the release of NF-kB, pro-inflammatory cytokines and chemokines are released including interleukin-6, interleukin-1-beta, tumor necrosis factor-alpha along with neutrophils and monocytes.
The last stage is resolution of inflammation. Redness, increased temperature, swelling, pain and loss of function at the site of injury/trauma is a result of the above cascade of events, which in time is resolved by the immune system with the help of anti-inflammatory cytokines and chemokines.5, 6