(Selected Tables and Figures referenced, but not present in this blog
can be found in their corresponding Science Version blogs)
Other than my ad nauseum repetition of “Chronic inflammation (CI) being the basis of all diseases,” our discussions up to this point regarding CI have really only referenced the relatively obvious disease categories of allergy, infection, and immune diseases that are existentially related to CI. So let’s take a look at some other highly prevalent disease categories (cardio/cerebrovascular disease, musculoskeletal disease and injury, and neurologic and neurodegenerative diseases) and see what their direct and indirect relationships might be to CI.
Several landmark clinical studies have been done on the role of CI in the incidence of heart attacks and strokes. The findings in the studies show that a sustained low level of inflammation promotes the accumulation of cholesterol or plaques in the coronary and cerebral arteries, serious problem called atherogenesis. This can trigger a continuing inflammatory response with the immune system interpreting these plaques as being abnormal and foreign, responding by creating a sort of barrier against them. Once this happens, the plaques loosen and blood clots and thrombi can cause heart attacks and strokes. Myocarditis, an inflammation of the heart muscle (myocardium), has also been shown to be a risk in infectious diseases, especially COVID-19. This can happen to those even with low blood cholesterol levels but who have elevated levels of inflammatory markers in the blood. A recent clinical trial proved that targeting inflammation without changing cholesterol levels can have a significant impact in reducing the likelihood of heart attacks and strokes by 15%.
Data have shown that inflammation has a central and stimulating effect on the development of atherosclerosis leading to increased risk of cardiovascular disease (CVD). Factors that produce dysfunctions in blood vessel walls (remember that effect as one of the causes of CI in Blog #13?) create cellular accumulations and increased production of tumor necrosis factor (TNF-a) and other interleukins (ILs) associated with the CI process and this becomes yet another cause of plaque formation (atherogenesis). There is strong evidence that anti-inflammatory biologic drugs, such as anti-TNF-a and anti-IL-6 agents, could control atherogenesis and ameliorate CVD risk. New research shows that reduced mortality and morbidity using biologic anti-IL-1b therapy to treat men and women who have had a prior heart attack provides proof of CI as contributing to the development of CVD.
In furtherance of my hypothesis of all diseases being derived from CI, consider the fact that acute inflammation secondary to injury, when not treated early (and sometime even when treated), will convert into CI (e.g., arthritis, bursitis) and the inexorably associated physical (musculoskeletal) “…itis” (inflammation) syndromes. Such conditions (excluding congenital and degenerative “disorders”) are conversions from their primary cause like physical injury, etc. to immunologic disease and resultant CI. Finally, aging is the consequence of the steady, prolonged accumulation of cellular joint damage related to the failure of clearing necrotic and cellular debris over years. The increasing load of these “damage-associated molecular patterns” called DAMPS leads to the release of proinflammatory cytokines (IL-6 and IL-18) causing ongoing low-grade CI. The functional decline of the immune system, including reduction in the length of chromosomes with aging, is referred to as “immunosenescence” and the associated active inflammatory process is called “inflammaging.” The name implies a CI process and that’s “proof of concept” for CI being “the basis of all disease.” I’m sure you’re tired of hearing that by now. Sorry, but you’ll be hearing it a lot more.
Functions and dysfunctions involving the brain, called neurologic and neurodegenerative disorders or diseases, constitute the highly complex relationship between the immune system and the brain or central and peripheral nervous systems. This subject demands its own blog. So let’s make that our next topic for Blog #17, Neuroimmunology.
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