Chronic Inflammation: Real Disease, Wrong Name

Chronic inflammation is a term used by your grandmother and your doctor to mean something. I am confident that they are both talking about different things. There are two types of inflammation that are often muddled: acute and chronic inflammation. Acute inflammation is a beneficial immune response that is induced by tissue damage due to trauma or infection. Chronic inflammation, in contrast, is not part of the body’s healing process. When chronic inflammation occurs, a dysfunctional immune system and tissue damage become the new norm.

Acute Inflammation: the Immune Response for the Ages

Prior to modern medicine, our immune system was our only weapon to combat infection. Acute inflammation played a vital role in our ability to survive, functioning as our first and last line of defense. There are four classical signs of inflammation: calordolorrubor and tumor (latin for heat, pain, redness and swelling). Undoubtedly, these signs have been handed down by word-of-mouth since the beginning of man, but were first described in writing during the first century by the Roman medical writer, Aulus Cornelius Celsus, possibly the first “Renaissance Man” centuries before the Renaissance. Acute inflammation has been around a very long time indeed.

Acute inflammation comes up fast, is focused on eliminating harmful pathogens, and disappears as soon as its job is done. It is a beneficial immune response, attempting to eliminate harmful pathogens that can kill the host. Acute inflammation is a finely tuned immune response that benefits the patient by eliminating the source of the infection and returning the host to normal. Over the last dozen or so millennia, acute inflammation helped us survive long enough to reach a reproductive age. That is, the role of acute inflammation in fighting infection was to prolong the host’s life to allow successful propagation of the species.

Chronic Inflammation: A Disease of Modern Life

In stark contrast, chronic inflammation inhabits the time of life after reproductive activity is no longer essential for survival of the species (let’s say after 30 years of life). Unlike acute inflammation, chronic inflammation is a long-term dysregulated immune response that is destructive or maladaptive for the patient. When a patient lives with chronic inflammation for a long time, life expectancy is shortened with a negative impact on quality-of-life. From an evolutionary perspective, the shortened life span that occurs after peak reproductive years is irrelevant. Evolution does not care about what happens after we pass that peak but modern man does. Today, where life after 40 is long and fulfilling, chronic inflammation has become the bane to our existence.

The many diseases associated with chronic inflammation tend to appear later in life. For the most part, they are diseases of aging. The diseases of chronic inflammation combine with our famously sedentary, high-caloric lifestyle to form the perfect storm. We need to better understand the role chronic inflammation plays, and the threats it poses. Chronic inflammation is part of the pathophysiology of many chronic diseases including obesity, diabetes, cancer, cardiovascular disease, stroke, Parkinson’s disease, dementia and refractory depression. For example, chronic inflammation plays a vital role in cancer. Not only can chronic inflammation cause cancer, but when the cancer becomes established, it makes the cancer worse by causing increased mutation and promoting metastasis. We can find similar results in cardiovascular disease.

For 30 years, we have been told that elevated cholesterol levels are the cause of cardiovascular disease. But it isn’t that simple. In a recent study, a large multinactional pharmaceutical company studied patients at risk for cardiovascular events and found that chronic inflammation is as dangerous as elevated cholesterol. Over 4,000 patients with biomarkers of chronic inflammation and well-controlled blood lipids were randomized to placebo or treatment with a powerful anti-inflammatory drug. The patients who had their chronic inflammation controlled with the anti-inflammatory drug had better outcomes; in fact a lot better, due to decreased cardiovascular events and decreased risk of cancer. This is the first study to prove that reversing chronic inflammation will have measurable and important health benefits and may improve survival. I suspect this is the dawning of a new age.

Inflammation: It’s All About Knowing When to Hit the Brakes

Why is it that chronic inflammation sticks around while acute inflammation goes away once the problem is resolved? I believe the problem is twofold. First, chronic inflammation sets up a non-virtuous cycle where immune dysregulation worsens the pathology and causes more chronic inflammation that exacerbates the problem. That is why the cancer gets worse, why the patient that smokes has a higher risk of cardiovascular and Alzheimer’s disease and why the obese Type 2 diabetic has nonalcoholic fatty liver disease (NASH).

The second problem is that pesky Darwinian theory of evolution. Acute inflammation has an elegant biologic rheostat call resolution biology. The sole purpose of resolution biology is to put the brakes on the acute inflammatory response and turn it off before there is collateral damage. Chronic inflammation has no brakes. Since there is no evolutionary pressure to reverse the dysregulated immune response, there is no ‘resolution biology’ equivalent to rein in chronic inflammation. Instead, chronic inflammation is on-going and relentless, causing damage to its host by developing and perpetuating the chronic diseases that consume so much of our healthcare budget.

Can chronic inflammation be treated? The answer is sort of. Remember what your mother said, “…get your sleep, don’t worry, eat well, exercise, don’t smoke and don’t get fat.” If you do all of those things, you will have a leg up on reducing the risk of developing the many diseases associated with chronic inflammation. There is evidence demonstrating the effectiveness of pharmaceutical intervention, but these retrospective studies have not been designed or tested specifically to treat chronic inflammation. Consequently, it is difficult to make recommendations based on what we know today.

The Future is Bright

I predict there will be therapies tested and approved to treat chronic inflammation in the next five years or so. In fact, as medicine begins to recognize the human and financial cost of untreated chronic inflammation, chronic inflammation will become a “disease”. In the future, as part of our annual health check-up, the clinical team will look for signs and symptoms of chronic inflammation just like they look for hypertension, hyperlipidemia, elevated glucose and anemia today. There will be a test to determine if you “suffer” from chronic inflammation. If you have the disease, it will be treated by both lifestyle changes and pharmaceutical intervention. As we educate the public and the medical community about the dangers of chronic inflammation, people will get serious about treatment. The way I see it, once we lessen the burden of chronic inflammation, we will see a difference in people’s lives, improve the quality and length of life.

About the author:

Raymond J. Tesi, M.D., is CEO of INmune Bio, an immunotherapy company developing treatments to reprogram the innate immune system to fight disease.

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