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Inflammation may have started as the solution—for example, as a way to rid the body of a dangerous invader—but if it doesn't turn off when it should, it instead can become the problem.
To protect itself and try to remove the injurious stimuli, the body triggers the inflammation, an elaborate response involving the vascular system, the immune system, and various cells within the injured tissue.
The classic signs of inflammation — swelling, pain, redness and loss of function — usually appear after an injury.
The body's immune response may keep inflammation going, long after the threat has cleared. Acute inflammation has now transitioned to chronic inflammation.
Chronic inflammation plays a central role in some of the most challenging diseases of our time, including rheumatoid arthritis, cancer, heart disease, diabetes, asthma, and even Alzheimer’s.[13-15]
Oxidative Stress
Oxidative Stress
At the center of inflammation is the concept of oxidative stress, which is like a biological type of "rusting" of our organs and tissues. Oxidation is a normal part of everyday living, but oxidation in overdrive can become a problem.
This can happen both on the outside and the inside:
Outside
Can cause wrinkles and premature aging
Inside
Can stiffen our blood vessels, damage cell membranes, and essentially wreak havoc on our precious interior designs
Acute Inflammation
Acute Inflammation
In acute inflammatory response, a number of secreted molecules include:
C-reactive protein (CRP)
CRP is produced by the liver only during episodes of acute inflammation. It is highly correlated with obesity, cardiovascular diseases, diabetes, and cancers.
IL-6 is an important mediator of fever and of the acute phase response.
have been validated. However, in age-related chronic inflammation, no standard cytokine signature exists.[16,17]
There is abundant evidence that certain pro-inflammatory cytokines such as IL-1β, IL-6, and TNF-α are involved in the process of pathological pain.
Canonical acute inflammation proteins (CRP, IL-6, etc.) have also been associated with immunosenescence in previous studies.
Immunosenescence is the gradual deterioration of the immune system, brought on by natural age advancement. Generally, it is believed that the adaptive immune system is affected more than the innate immune system. Immunosenescence involves both the host's capacity to respond to infections and the development of long-term immune memory.
How Chronic Inflammation Develop?
How Chronic Inflammation Develop?
Inflammatory components of the immune system are often chronically elevated in aged individuals.
Contrary to the acute response, which is typically triggered by infection, chronic inflammation is thought to be triggered by physical, chemical or metabolic noxious stimuli (“sterile” agents) such as those released by damaged cells and environmental insults, generally termed “damage-associated molecular patterns” (DAMPs). This type of inflammation is associated with aging and characterized by being low-grade and persistent, ultimately leading to collateral damage to tissues and organs.[12,13]
Cytokines have an important function in the body, activating the immune system to fight infection. But because they work by an inflammatory process, when they’re overproduced they put the body into a state of chronic inflammation, which causes cells to age faster. Chronic inflammation can develop in several ways:
Threat remains
The immune system is pretty good at eliminating invaders, but sometimes pathogens resist even our best defenses and hide out in tissues, provoking the inflammatory response again and again.
Autoimmune disorder
The immune system goes into "threat mode" when no true threat exists. It reacts against the joints, intestines, or other organs and tissues as if they were dangerous. As the inflammatory response continues, it damages the body instead of healing it.
Unhealthful lifestyle
Smoking, failing to exercise regularly, or eating a diet high in refined carbohydrates can contribute to chronic inflammation. For example,
Those on a “high-salt diet displayed a markedly higher number of monocytes,” which are a type of immune cell you often see increased in settings of chronic inflammation and autoimmune disorders.[9]
Symptoms of Chronic Inflammation
Symptoms of Chronic Inflammation
The signs of chronic inflammation are not as obvious as those of acute inflammation. No sharp twinge of pain as when you cut yourself, no swelling or redness will you see to alert you to a problem.
Chronic inflammation can be widespread or more localized to specific areas of the body. Therefore the symptoms can vary considerably, such as:
Fatigue and lack of energy
Depression, anxiety
Muscle aches and joint pain
Constipation, diarrhea, and other gastrointestinal complaints
Changes in weight or appetite
Headaches
Brain fog (a "fuzzy" mental state)
Chronic inflammation and Diseases
Chronic inflammation and Diseases
Your joints
Your joints
When you suffer a joint injury — maybe a banged-up knee or a twisted ankle — a little inflammation is part of the healing process. Puffy, red, tender joints may indicate that your immune system is working to remove damage and promote the growth of new tissue, a healthy kind of inflammation. But sometimes the immune system launches unhealthy, chronic inflammation in the joints, for no apparent reason. This leads to pain, stiffness, and joint damage known as inflammatory arthritis.
Your Heart
Your Heart
The buildup of inflammation — not necessarily cholesterol — is what can lead to a heart attack.[24]
Inflammation in the artery wall is the real cause of heart disease
Without inflammation, cholesterol would move freely throughout the body as nature intended. It is inflammation that causes cholesterol to become trapped.
The actual sequence of actions that takes place beginning with inflammation and ending in an actual heart attack is complex (read [6] for details), involving changes to the coronary artery and blood vessels that nourish the heart, but the outcome is the same: an increased risk for a life-threatening cardiovascular event.
Figure 1. Overview of cellular and molecular processes that govern inflammation and its resolution (Source: [24])
Resolution of Inflammation
Resolution of Inflammation
To prevent progression from acute inflammation to cchronic inflammation, the inflammatory response must be suppressed to prevent additional tissue damage. Inflammation resolution is a well-managed process :
Involves the spatially- and temporally-controlled production of mediators
During which chemokine gradients are diluted over time.
Circulating white blood cells eventually no longer sense these gradients and are not recruited to sites of injury.
Dysregulation of this process
Can lead to uncontrolled chronic inflammation
Inflammation resolution processes that rectify tissue homeostasis include reduction or cessation of tissue infiltration by neutrophils and apoptosis of spent neutrophils, counter-regulation of chemokines and cytokines, macrophage transformation from classically to alternatively activated cells, and initiation of healing.
Conclusions
Conclusions
Inflammation is traditionally defined by its cardinal signs—redness, swelling, heat, and pain—which are induced by infection or tissue injury. But a growing body of evidence shows that inflammatory cells and mediators are also important for homeostatic functions, such as metabolism, tissue remodeling, and interorgan cross-talk.[26]
Inflammatory cells and molecules play important roles in acute responses to infection as well as to tissue perturbations. Thus, inflammation exists on a spectrum that can be tuned up or down, depending on the context.
Inflammatory responses exhibit substantial variability among individuals. Our growing understanding of the ubiquitous nature of inflammation and its diverse roles will benefit a wide range of efforts to treat, prevent, and ameliorate disease.
References
References
The impact of nutrition on COVID-19 susceptibility and long-term consequences
Anti-inflammatory effect and mechanism of proanthocyanidins from grape seeds.
Researchers identify key protein involved in triggering inflammation
An Inflammatory Clock Predicts Multi-morbidity, Immunosenescence and Cardiovascular Aging in Humans
Inflammatory responses and inflammation-associated diseases in organs (Good)
Goldberg, E.L., and Dixit, V.D. (2015). Drivers of age-related inflammation and strategies for healthspan extension. Immunological reviews 265, 63-74.
Kotas, M.E., and Medzhitov, R. (2015). Homeostasis, inflammation, and disease susceptibility. Cell 160, 816-827.
Crusz, S.M., and Balkwill, F.R. (2015). Inflammation and cancer: advances and new agents. Nature reviews Clinical oncology 12, 584-596.
Liu, C.H., Abrams, N.D., Carrick, D.M., Chander, P., Dwyer, J., Hamlet, M.R.J., Macchiarini, F., PrabhuDas, M., Shen, G.L., Tandon, P., et al. (2017). Biomarkers of chronic inflammation in disease development and prevention: challenges and opportunities. Nature immunology 18, 1175-1180.
Franceschi, C., Garagnani, P., Vitale, G., Capri, M., and Salvioli, S. (2017). Inflammaging and ’Garb-aging’. Trends in endocrinology and metabolism: TEM 28, 199–212.
Morrisette-Thomas, V., Cohen, A.A., Fulop, T., Riesco, E., Legault, V., Li, Q., Milot, E., Dusseault-Belanger, F., and Ferrucci, L. (2014). Inflamm-aging does not simply reflect increases in pro-inflammatory markers. Mechanisms of ageing and development 139, 49–57.
Epel, E.S., B. McEwen, T. Seeman, et al. Stress and body shape: Stress-induced cortisol secretion is consistently greater among women with central fat. Psychosomatic Medicine 2000:62(5):623-32.
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