Other than my ad nauseum repetition of “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 (atherogenesis). This can trigger a continuing inflammatory response wherein these plaques are perceived by the immune system as abnormal and foreign to which they then respond by creating a sort of barrier. Once this happens, loose plaques and blood clots may be the cause of heart attacks and strokes. Myocarditis, an inflammation of the heart muscle (myocardium), has 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 called CANTOS (Canakinumab Anti-Inflammatory Thrombosis Outcomes Study) 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 inciting role in the development of atherosclerosis leading to increased cardiovascular disease (CVD) risk. Factors such as endothelial dysfunction, macrophage accumulation, and production of tumor necrosis factor (TNF-a), IL-1, and IL-6 associated with the CI process lead to 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 the pathogenic contribution of inflammation in 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” syndromes. Such conditions (excluding congenital and degenerative “disorders”) are conversions from their primary etiologies (physical injury, etc.) to immunologic pathogenesis and resultant CI. 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 (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 as “inflammaging.”
Neurologic and neurodegenerative diseases are one part of the highly complex relationship between the immune system and the neurological (central and peripheral) systems. This subject demands its own blog. So let’s make that our next topic for Blog #17, Neuroimmunology.
Discussion Questions:
CI plays a central role in atherosclerosis through the process of atherogenesis. What is the sequence of immunologic events that can produce heart attacks and strokes?
The functional decline of the immune system with aging is referred to as “immunosenescence” and the associated active inflammatory process as “inflammaging.” What are the characteristic proinflammatory cytokines associated with this aging process?
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