The answer to that question is “both!” When inflammation occurs as the result of an injury, it’s not agreeable, but it’s definitely beneficial, so we can classify it as a friend. This type of inflammation is almost always acute inflammation, which means that it only lasts as long as needed for healing purposes.
But sometimes inflammation takes place in response to a number of different stimuli, some of which emerge as the result of an internal malfunction of some kind, and some of which arise for no discernible reason. This type of inflammation can persist for months or even for years, and is termed chronic inflammation. Chronic inflammation can result in a range of harms to our overall health and function, and is definitely not beneficial.
The word “inflammation” comes straight from the Latin word “inflammation,” spelled exactly the same way. It has been recognized for at least 2,500 years. Hippocrates, in the 5th century BC, used the term edema in his description of the healing process, and Aulus Celsus, who lived just around the beginning of the first century AD, described the four signs of inflammation as rubor (redness), tumor (swelling), calor (heat), and dolor (pain). Inflammation comes from the Latin word flamma, thus inflammation essentially means “setting on fire,” and everyone one who has sustained just about any kind of injury knows what that feels like.
According to my OED, the earliest use of the word “inflammation” in English was in 1533. Here’s their quote: “Much sleepe augmenteth heate, more than is necessary, whereby hot fumes and inflammations are often engendered.” That does not sound like what we currently call inflammation. Whoever made that statement was obviously looking for a cause, but linking inflammation with heat was obviously correct.
When we sustain an injury, even a minor injury, the inflammatory process gets underway as a friend (not a foe!), essentially as part of the healing process. Let’s say you scraped your leg while climbing over a stone wall. The scrape only slightly broke the skin, and there was just a bit of bleeding, but the impact was painful. That little injury triggers a sequence of events, beginning with a considerable increase in local blood flow. The capillaries become more permeable, resulting in the build-up of fluid in the space in and around muscle and nerve fibers. A large number of cells of different types are summoned to the area, and these immediately go to work to clean up the mess. Damaged tissue is devoured and carried off by macrophages and neutrophils, and the process of replacing dead cells with new cells begins. The entire area of the injury is walled off, so as to prevent the spread of any invading pathogens. And, yes, even though your skin was only slightly broken, pathogens certainly did enter. That’s because your skin (no matter how scrupulous you are about personal hygiene) is colonized by immense numbers of microbes of various kinds, especially staphylococci, which are primed to attack your cells. The inflammatory process is highly efficient at preventing the spread of staph infections that invade in that way. Once the infection has been contained by this walling-off process, your own immune system will wage war on the invading pathogens, and in most cases, your immune system will achieve victory in this war.
That summary of the way inflammation responds to an injury describes the beneficial effects of inflammation – i.e., that aspect of inflammation that qualifies it to be a friend. But it wasn’t until the late 19th century that some of the harmful actions of inflammation came to be understood.
The German scientist Rudolf Virchow observed that there was a fifth sign of inflammation, that being a loss of function in the affected area. Virchow described short-term inflammation as the body’s pathway to healing. The process of inflammation included the release of nutrients from damaged blood vessels and the attraction of a number of cells to the site of the injury or disease. Virchow also pointed out that inflammation could arise not only from external injury, but from pathologies affecting a person from within.
Virchow was perhaps the earliest scientist to surmise that while short-term inflammation was an aid to healing, long-term or chronic inflammation could result in damage to the affected person. This damage, in Virchow’s view, could include the development of cancer.
Acute inflammation, resulting from an injury, can morph into chronic inflammation. We’ll take a look at how it develops, what factors might be the causes, the harms it brings, how it might be prevented, and how it might be able to be treated.
The mechanism of chronic inflammation is essentially the same as that in acute inflammation. The essential difference is that acute inflammation recedes as the injury heals, while chronic inflammation hangs around as long as the conditions that caused it remain unchanged. We might also call those conditions that lead to chronic inflammation “injuries,” and in a sense they are. Obesity, which as we’ll see is one of the conditions that bring on chronic inflammation, might be called an “injury” to our system. But while acute inflammation plays an important part in the healing of an injury, chronic inflammation does nothing to reduce obesity.
One could say that the reason the inflammatory process results in redness, swelling, heat, and pain is that inflammation confines and concentrates the injury to a relatively small area, like waging an all-out war on a single small battlefield.
And, naturally, as in any war, there is collateral damage. If the inflammation occurs as a result of a bruise or a minor skin infection, the collateral damage will be minor. But if, on the other hand, inflammation occurs as a response to some type of internal disruption or as a reaction to certain types of stimuli, the collateral damage can be considerable. And, in some cases, inflammation seems to occur spontaneously, not in response to injury or a specific stimulus. In those cases, the inflammatory process in itself constitutes the disease.
Mediators of inflammation
The very word “mediators” in that context is a bit confusing, at least to the non-medical reader. Most people think of mediators as the folks who try to resolve differences between two warring parties, like the opposite sides of a lawsuit or labor unions versus management. In medical terms, the mediators are the agents that trigger the response, period. There is no give-and-take.
The numbers of inflammatory mediators are legion. They can be relatively simple molecules or living cells. Some of the ones whose names some readers might recognize include histamines, serotonin, prostaglandins, bradykinins, a number of cells carried in the bloodstream such as macrophages and neutrophils, B-cells, T-cells, lymphokines, caspases, and many, many others. A number of factors also stimulate generation of granulocytes and monocytes by the bone marrow; these include tumor necrosis factor (TNF), which is one of the drivers of rheumatoid arthritis (RA).
It’s easy to see what the larger cells and molecules are doing. For example, scientists can actually watch macrophages in action. Besides cleaning up the mess that occurs when pathogens invade and create an infection, macrophages are capable of pumping out many different small molecules that also contribute to the inflammatory process.
A large category of inflammatory mediators are classified as cytokines, although by no means are all cytokines pro-inflammatory. Cytokines do not engulf and gobble up bacteria or cells. Instead, they may interact chemically with receptors on the surface of these bodies, or they may pass through openings in their coating. These actions depend on the precise shape of the molecules and on their binding properties. Sometimes a molecule fits neatly into receptors on the surface of a cell, thereby inactivating the receptor. The activity of some of these molecules may be conceptually simple, but detecting and understanding that activity is far from simple.
An essential motive for striving to understand the mechanisms of inflammation is that inflammation is one of the factors that lead to atherosclerosis, which, as we know, is a fundamental cause of cardiac disease. That inflammation contributes to atherosclerosis may come as something of a surprise, in view of the well-established fact that the primary cause of atherosclerosis is the deposition of low-density cholesterol in the walls of our arteries.
Cholesterol doesn’t just swim around in the bloodstream. It actually works its way into the arterial wall. This constitutes a kind of insult to the arterial wall and provokes an inflammatory response, which in turn results in the formation of blood clots. It is these blood clots that, at least in some cases, block coronary arteries, causing heart attacks, and also block cerebral arteries, causing strokes.
It has been known for about 30 years that a certain number of individuals who have “normal” cholesterol levels nonetheless experienced the same kind of cardiac events as persons with elevated cholesterol. But it was found that these persons, who do not have cholesterol at levels that had been associated with heart disease, do have elevated levels of C-reactive protein (CRP), which for more than 80 years has been known to be associated with generalized inflammation.
So the chain of events seems to be that to some degree C-reactive protein may be an underlying cause of heart disease, and that C-reactive protein levels increase in persons who are experiencing inflammation. Whether we can say that inflammation is an underlying cause of heart disease is not definitely settled, but there is clearly an association.
Chronic inflammation produces a range of effects in our bodies beyond the traditional signs of redness, swelling, heat, and pain. These can include the following:
Fatigue and lack of energy
Depression and anxiety
Muscle aches and joint pain
Constipation, diarrhea, and GI complaints
Change in weight or appetite
Headaches
Fuzzy mental state
The inflammatory process is the same, whether we’re talking about acute inflammation or chronic inflammation.
Chronic inflammation
In contrast with acute inflammation, chronic inflammation – as the term implies – is not short-lived. And, also in contrast with acute inflammation, it is rarely helpful. Although it may begin with the same cellular activity as acute inflammation, it morphs into a lingering state that persists for months or years.
Chronic inflammation is a slower but more insidious process than acute inflammation, and it has been linked to a number of serious diseases, including heart disease, stroke, type 2 diabetes, cancer, chronic obstructive pulmonary disease (COPD), Alzheimer’s disease, and arthritis. These diseases are the leading causes of death on Planet Earth. Three out of five people around the world die from diseases that are linked with chronic inflammation.
(I should emphasize that the crucial word in that statement is “linked.” My data comes from a Harvard Medical School document about inflammation. I don’t question the accuracy, but perhaps the authors gave undue emphasis to the risks of chronic inflammation. A better way of putting it might be “sometimes associated with.”)
In chronic inflammation, what may have started as the solution – for example, as a way to rid the body of a dangerous invader – instead becomes the problem. Chronically inflamed tissues continue to send out alarm signals that trigger the body’s immune response long after the threat has subsided.
When white blood cells heed the call and arrive at the scene, they sometimes attack healthy tissues and organs, further amplifying the response and setting the stage for a persistent inflammatory state.
As a result of this process, more tissues are attacked and destroyed instead of entering a healing process. For example, when pro-inflammatory cells remain in the blood vessels, they promote the build-up and deposition of sticky arterial plaque. This is the same plaque that contributes to cardiovascular diseases. But our immune system detects this arterial plaque as a foreign invader, and deploys yet another army of first responders.
Chronic inflammation can develop in any of several ways. One possible avenue is that the body is unable to rid itself of an offending substance, whether it is a pathogen, some kind of irritant, or a dangerous chemical toxin. Our immune system is usually highly efficient at eliminating invaders of any stripe, but sometimes pathogens resist even our best defenses and conceal themselves in our tissues, repeatedly provoking the inflammatory response. And chronic inflammation may be the result of the body’s failure to effectively break down and remove damaging chemicals.
A likely cause of chronic inflammation is that our body suspects the presence of some offending substance that it can’t manage to expel or neutralize. When that happens, the immune system goes into “threat mode”, which can result in chronic inflammation, even if no actual autoimmune disorder is present.
In an autoimmune disorder, the immune system seems to become overly sensitized to the body’s own healthy cells and tissue. 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.
Acute respiratory distress syndrome (ARDS) is another example of an overreaction of inflammation. ARDS can emerge when a person experiences trauma that directly affects their lungs, such as severe pneumonia, having water invade the lungs, or inhaling smoke or noxious gases. The immune system dispatches cells that can be helpful in many forms of trauma. The cells signal the blood vessels to leak fluid, which is the normal response to traumas like bruises and scrapes. But when the fluid passes into the lungs, it clogs the alveoli, which are the little sacs that transport oxygen into the bloodstream. The inflamed alveoli block the oxygen from getting into the blood, which means that breathing stops functioning normally. ARDS requires urgent medical care, and in some cases can be fatal.
The diseases linked to chronic inflammation are legion. No part of the body is immune. Inflammation affects the brain and spinal cord, leading to Alzheimer’s disease, Parkinson’s, and multiple sclerosis. In the lungs it can bring on allergies, asthma, chronic obstructive pulmonary disease, and lung cancer. It can contribute to kidney failure, nephritis, hepatitis, atherosclerosis, inflammatory bowel disease, ulcerative colitis, macular degeneration, rheumatoid arthritis, and numerous other diseases. It is by no means the single cause of these diseases, but in most cases the inflammatory response aggravates the disease.
Causes of chronic inflammation and potential treatments
As we know, some lifestyle choices are not healthy. Smoking is at the top of the list, and diet probably plays a large part. Some healthcare practitioners make definitive pronouncements about what we should and shouldn’t eat, but I am hesitant to go into diet issues in any detail. On the most general level, the accepted wisdom seems to be to avoid highly processed foods, especially carbohydrates, and also sugary soft drinks. Transfats get the red flag, including margarine and non-dairy coffee creamers. Many oils get a warning because of Omega 6 fatty acids, but olive oil is an exception. A sedentary life style also may contribute to chronic inflammation.
I should not have to go into detail as to what choices would discourage chronic inflammation: in general terms, a diet that emphasizes fruits and vegetables and an active lifestyle. As we know, those choices point to the standard recommendations for general health and have no specific connection with inflammation, whether acute or chronic.
However, there are medications that can be specifically used to alleviate chronic inflammation. They all have their plusses and minuses, but on balance they are beneficial. Four classes of drugs are commonly used to treat inflammation – nonsteroidal anti-inflammatories (NSAIDs), corticosteroids, immunosuppressants, and biologics.
NSAIDs specifically target inflammation by inhibiting prostaglandins, which are a group of compounds that cause inflammation. Prostaglandins are among the specific mediators of inflammation that we discussed earlier. A widely used NSAID is ibuprofen, which is available over the counter (OTC) as Advil and Motrin. Naproxen, sold OTC as Aleve, is somewhat more powerful than ibuprofen. Strictly speaking, aspirin is also an NSAID. Like all drugs, taking NSAIDS incurs risks, especially when taken long-term to manage a chronic condition. These risks include gastric bleeding, stomach ulcers, and cardiac issues.
Immunosuppressants specifically suppress the immune response (as their name suggests) by inhibiting the production of the substances in our system that promote inflammation. This class of drugs includes methotrexate (Rheumatrex, Trexall) and tofacitinib (Xeljanz). Many diseases can be quelled by this class of drugs, including rheumatoid arthritis, inflammatory bowel disease, lupus, or psoriasis. The drugs also reduce the body’s ability to fight infection, so anyone using them should be monitored very carefully.
Corticosteroids are synthetic drugs that mimic cortisol, a natural hormone that has an anti-inflammatory effect. Common corticosteroids include prednisone, hydrocortisone, dexamethasone and triamcinolone. These agents are used to treat a range of diseases, such as asthma, allergies, and autoimmune diseases that can result in chronic inflammation. They can have significant side effects such as bone thinning and weight gain, and also have negative effects on the patient’s sense of well-being. Corticosteroids are best used temporarily.
Biologics are derived from living cells, although they are produced synthetically. Examples are adalimumab (Humira), infliximab (Remicade), and etanercept (Enbrel), which are primarily used to treat rheumatoid arthritis. Their mode of action is targeting the specific agents or cells in the body that promote inflammation. Biologics are more selective than immunosuppressants; however, because they interfere with the immune system, they also reduce the body’s ability to combat infection.
Yes, there are drugs that can help us push back against chronic inflammation, but as we see, they all have drawbacks and need to be used prudently. With the help of a healthcare provider, we have to balance the potential benefits of combating chronic inflammation against the potential harms of drug treatment. Of course, this is true of any disease or adverse health condition.
Treating acute inflammation is a different story altogether. Most of the time, there is no need to treat acute inflammation, since it emerges as a response to an injury to the body, whether external or internal, and – again, most of the time – the effect is beneficial.
But chronic inflammation is associated with a large range of diseases and adverse conditions, and is implicated in a large fraction of global mortality. So treating chronic inflammation is essential. The benefits of treating chronic inflammation greatly outweigh the harms. Because the harms of chronic inflammation are not immediate, it’s easy to put off starting on course of treatment. But in my opinion, we should keep an eye on some of those factors mentioned above that might point to chronic inflammation. For emphasis, I will repeat them here: fatigue, depression, muscle aches, GI complaints, change in appetite, headaches, or a fuzzy mental state. Better to try to deal with them than to ignore them.
More about AI
The previous Doc Gumshoe installment focused on the role of AI in healthcare – highly valuable in that it can enable physicians to access a huge range of information on symptoms and the effects of an immense number of pharmaceutical agents on an immense number of human cells and organ systems, but in no way a substitute for patient-physician interactions.
The subject I want to raise here is the changes that AI may bring to the health of the human race as a whole. There are alarm-sounders that suggest that AI will lead to the extinction of the human race. I am by no means in that category. But I do believe that AI will have profound effects on human cognition.
Here is an excerpt on that subject from a recent The New Yorker magazine article:
“An example: I recently attended a scholarly talk on a rare illuminated manuscript. The speaker was as eminent as they come, but the talk was not easy to follow. Frustrated, I opened ChatGPT and started asking it questions about the subject. In the course of that disappointing lecture, I had a rich exchange with the system. I learned what was and wasn’t known about the document, who had done the foundational research, and how scholars had interpreted its iconography and transmission. Was the information perfect? Surely not, but neither is what we get from people. Was it better than the talk I was hearing? By a wide margin.
“Increasingly, the machines best us in this way across nearly every subject. Yes, you will hear the true erudites explain that DeepSeek can’t reliably distinguish Karakalpak from adjacent Kipchak-Nogai dialects (or whatever the case may be). This feels to me like pointing at daisies along the train tracks as an actual locomotive screams up from behind. I’m a book-reading, book-writing human—trained in a near-monastic devotion to canonical scholarship across the disciplines of history, philosophy, art, and literature. I’ve done this work for more than thirty years. And already the thousands of academic books lining my offices are beginning to feel like archeological artifacts. Why turn to them to answer a question? They are so oddly inefficient, so quirky in the paths they take through their material.
“Now I can hold a sustained, tailored conversation on any of the topics I care about, from agnotology to zoosemiotics, with a system that has effectively achieved Ph.D.-level competence across all of them. I can construct the ‘book’ I want in real time—responsive to my questions, customized to my focus, tuned to the spirit of my inquiry. And the astonishing part is this: the making of books such as those on my shelves, each the labor of years or decades, is quickly becoming a matter of well-designed prompts. The question is no longer whether we can write such books; they can be written endlessly, for us. The question is, do we want to read them?”
And from Princeton Professor D. Graham Burnett: “Literacy is a historical aberration no longer fit for this world. No point in asking students to read books.”
Where does that leave us poor humans? Ignorant and unintelligent, a docile species fit only for manual labor.
Humans created the arts and sciences. Humans created civilization, with all its many faults. What humans have accomplished has required a high degree of active intelligence. If we surrender the tasks of active thinking to AI, the arts and sciences and civilization itself will decline.
I do not believe AI will lead to the extinction of the human race, but I do not want to see thought and creativity turned over to AI. I want my fellow humans to go on exercising their brains to the utmost and continue human accomplishments in all matters and all realms. I am an optimist, and I trust that my fellow humans will employ AI as a servant and continue to think on their own.
