Acute Inflammation (Good) vs. Chronic Inflammation (Bad)

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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.^[13-15,27]

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

Video 1.  Foods That Cause Inflammation (YouTube link)

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-1β
• IL-6
• IL-6 is an important mediator of fever and of the acute phase response.
• TNF-α

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?

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:

1. 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.
2. 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.
3. 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

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

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

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

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

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

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3. Feeling Beat Up After Workouts? 5 Superfoods May Help
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6. Inflammatory responses and inflammation-associated diseases in organs (Good)
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9. Sodium and Autoimmune Disease: Rubbing Salt in the Wound?
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13. Kotas, M.E., and Medzhitov, R. (2015). Homeostasis, inflammation, and disease susceptibility. Cell 160, 816-827.
    
14. Crusz, S.M., and Balkwill, F.R. (2015). Inflammation and cancer: advances and new agents. Nature reviews Clinical oncology 12, 584-596.
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16. 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.
17. 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.
18. Oregon University Linus Pauling Institute
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20. The End of Illness by David B. Agus, MD
21. Common Drug Has The Potential To Slow Aging, Boost Cancer
22. Bowel Disease Increases Risk for Stroke and Heart Attack
23. WORLD RENOWNED HEART SURGEON SPEAKS OUT ON WHAT REALLY CAUSES HEART DISEASE
24. The Truth about Cholesterol (Travel to Health)
25. Resolution of Inflammation: What Controls Its Onset?
26. Inflammation: An expanding view
27. Common Pathophysiology in Cancer, Atrial Fibrillation, Atherosclerosis, and Thrombosis: JACC: CardioOncology State-of-the-Art Review