Inflammation is a natural part of the healing process, but when it goes on for too long, it becomes a cause for concern.
Inflammation is not unhealthy, it is just a natural response to a threat. It is a necessary part of fighting infections and preparing damaged tissues for healing. But if this process gets out of control, it can lead to several chronic diseases.
A leading cause of death in the developed world, coronary heart disease, has an inflammatory component. Chronic inflammation has also been identified in several cancers, as well as type II diabetes, inflammatory bowel disease, obesity, and Alzheimer’s disease.
This article explains the two different faces of inflammation: the healthy acute response to a threat, and the disease-associated chronic reaction. Here’s what we’re going to explain in this article:
- Immune system 101
- Where does inflammation start?
- Adaptive and innate immune functions
- How does chronic inflammation work?
- Obesity and chronic inflammation
Despite its notoriety in the headlines, inflammation is a healthy reaction to molecular danger signals, infection, or damage.
After a cut, we rinse and disinfect the wound, put on a bandage, and let it heal. Our immune system follows the same routine when we damage our body. It removes any infection, and clears up the damaged, infected, and dead cells to ensure that nothing interrupts the healing process.
Similar to an ambulance or police, our immune cells need to be alerted to damage. A complex system of chemical signals delivers the message and induces changes in the local tissue. It’s called inflammation, and it’s what recruits our immune cells to problem areas.
Inflammation is a healthy response that lacks appreciation because of its side effects: swelling, pain, and itching. All these sensations are essential: initial discomfort and itching makes us remove any dirt from a wound, and the lingering pain prevents us from disturbing the healing.
Inflammation starts when an immune cell recognises a molecule associated with damage, stress, or infection.
Inflammation is a cascade of events: every cell that receives a warning reacts and passes it on. As in every chain reaction, there is a starting point. Inflammation is started by a cell that recognises molecules associated with damage or infection.
If a cell suddenly dies, it releases chemicals that normally stay inside of it. For example, several strands of DNA floating around are a sign of damage. Local immune cells have DNA-specific receptors which recognise the DNA molecule when it is captured.
Some molecules produced by bacteria and viruses have unique structures.They can often be shared by several microorganisms. These chemicals often have important functions, so many species rely on very similar molecules.
Great podcast on "Eating for Inflammation" by the Doctor's Kitchen
The immune system uses molecular patterns to detect bacteria and viruses. For example, lipopolysaccharide is molecule that composes the cell walls of some bacteria. The immune system can use this to recognise whether the bacteria constitutes a threat.
When an immune cell senses one of these danger signals, it releases pro-inflammatory signalling molecules. This causes several changes around the tissue, which isolate the danger and allow to bring in more immune cells.
Our blood contains numerous immune cells waiting for a danger signal, but the blood vessels only have tiny holes that keep the cells from trespassing, a bit like fish in a net. When immune cells are recruited, these cells cause some damage to the tissue at the site of inflammation during their hunt for unwelcome guests.
As the immune system fights the infection and removes dying cells, the danger signals start to dim. Pro-inflammatory chemicals and immune cells leave the scene to anti-inflammatory colleagues, who initiate the repair but may leave some scarring. Soon enough, local order is restored, inflammation is resolved, but the tissue loses some of its integrity during the repair process.
Our immune response has two phases: rapid reaction from the innate immune system localises the threat until the potent adaptive immune system is ready to clear the infection.
The molecular patterns described above start the initial quick and robust immune response. Doctors call it innate immunity, and it uses non-specific defense mechanisms to localise and initiate a response to any detected threat. But it’s often not sufficiently potent or targeted to stop it.
Cells of your immune system hang around, waiting for danger signals
As the first responders of the innate immune system slow down the progression of an illness, the body’s heavy artillery gets ready for combat. The cells of the adaptive immune system are trained to recognise the infectious organism with exceptional specificity and sensitivity.
The body’s cells produce proteins, and adaptive immune system cells can distinguish between different pieces of foreign and human proteins. These pieces, called antigens, are very similar, and a mistake can cause damage to our body.
The system works the same for foreign invaders. Protein antigens are often unique to an infectious species, allowing exceptional potency and specificity of the response once immune cells have learned to recognise them.
But this also means that there are millions of potential antigen structures. The adaptive immune system needs to generate millions of different receptors to learn how to recognise good from bad, and normal from abnormal.
Receptor diversity comes from rearranging genetic blueprints. The cells that produce dysfunctional versions or recognise human protein pieces do not survive. The remaining adaptive cells stay in our bodies, waiting for an antigen that they recognise.
Adaptive immunity takes up to a fortnight to fully develop a potent and specific response. This is the time it takes to complete “training”, which involves finding the adaptive cells with right receptors and expanding their numbers.
This explains why symptoms of a common cold or flu typically disappear in under two weeks. The infection is causing illness because the innate immunity can not fully control it. But once an adaptive response is trained, it clears the unwelcome guests in a few hours.
After the immune cells are trained to recognise an infection, they linger in the body for years. If the same threat is encountered again, adaptive immunity can quickly respond and prevent the illness. This feature is called immunological memory, and it is central to vaccination.
A vaccine contains a mixture of infection antigens and a stimulating chemical to alert the innate immune system. Then, a brief inflammatory response induces adaptive immune cell training. Immune memory may take several injections to form, but it protects from the disease for a long time.
Chronic inflammation begins without an infectious trigger. By recognising and attacking a false target, it accelerates the progression of multiple diseases.
Inflammation is induced by cell damage or an acute infection. The immune response starts to weaken and resolves once the initial danger is removed. But sometimes the inflammation does not resolve and persists at a low level for years.
How does it work?
Atherosclerosis is a condition characterised by the build-up of plaque inside the arteries that transport blood from the heart to tissues. It is also known as “hardening of the arteries” because they become less flexible and lose their ability to adapt to changes in blood flow.
Our arterial walls begin to thicken as early as 15 years old. They develop atherosclerotic plaque (or lesions) that mainly consists of cholesterol and fat. These lesions can be found in almost every adult, and they progress with age.
In healthy people, this plaque is harmless, yet coronary heart disease is the leading cause of death worldwide. It can take decades before things go wrong. The plaque can break off and cause a blockage, or it can open and cause a blood clot to form, preventing blood flow to a vital organ. Both situations can lead to a heart attack, a stroke, or chronic kidney damage.
Atherosclerotic plaque growth is influenced by many factors - so many that we’ve created a table to list them all. But, it took scientists many years to understand how inflammation contributes to atherosclerosis.
|Smoking||High blood pressure|
|Diabetes type 2||Low physical activity|
|Obesity||High-fat, high-sugar diets|
Early plaque in the aorta is quite harmless, almost invisible - a consequence of the transport of lipids, molecules of fat, across the blood vessel walls. Normally, this process provides tissues with nutrients, but thick arterial walls can trap the lipids inside.
Great animated short about how stress affects your body by TED
These molecules of fat become oxidised, and that changes their structure, making them seem foreign to our body. Because arterial walls are always under stress from high blood pressure, they “overreact” to the accumulating lipids. They recruit immune cells to deal with the problem, initiating inflammation.
Unfortunately, our immune cells can only deal with a certain amount of lipids at once. They recognise oxidised molecules as a threat and secrete more pro-inflammatory factors. But there is no mechanism to remove accumulated lipids and cholesterol from the arterial wall.
Immune cells ingest too much cholesterol and die, which recruits new ones, and because there is always a danger signal, the inflammation does not resolve. It persists at relatively low levels and facilitates plaque growth. Later, the healing processes kick in, but they only worsen the situation.
Arterial walls have to be elastic to withstand the high blood pressure from the heart. When smooth muscle cells from the middle layer of the arterial wall respond to inflammation, they migrate to the “wound”. In an attempt to cover it up, they form a stiff cap over the plaque.
When this happens, the artery starts to lose its flexibility. It becomes harder for the vessel wall to adapt to the physical stress of the blood pressure. Subsequently, arterial walls have to deal with stronger forces, which increases the chances of plaque rupture.
Atherosclerosis is an example of what is called “sterile inflammation”. When it begins, there is no infectious trigger or serious tissue damage. The misguided immune response does not resolve because the trigger remains, and thus over extended periods, ends up contributing to disease progression.
When the body stores too much fat, it can lead to inflammation. That's why obesity and body mass are concerns for doctors.
Chronic inflammation is not a localised issue: when blood levels of pro-inflammatory molecules increase, chronic disorders progress faster. For instance, there is significant evidence that obesity is linked to atherosclerosis, cardiovascular disease, cancer risks, insulin resistance, and type II diabetes.
The problem lies in chemical signals produced by fat cells, called adipocytes. Excessive adipose tissue formed by fat cells secretes pro-inflammatory molecules in obese individuals. The mildly elevated inflammatory state includes increased blood levels of two potent molecules: TNF𝛂 and IL-6.
Tumour Necrosis Factor 𝛂 (TNF𝛂) is a pro-inflammatory chemical molecule secreted during inflammation that activates specific immune cells. TNF𝛂 is known to induce insulin resistance. It induces c-reactive protein (CRP) production in the liver - a diagnostic marker for chronic inflammation.
Interleukin-6 (IL-6) is an inflammatory signalling chemical molecule. High blood levels of IL-6 are associated with increased risk of several illnesses, including autoimmune diseases, which happen when the immune system directly attacks healthy cells, like coeliac disease and inflammatory bowel disease.
C-reactive protein (CRP) is an inflammation-associated protein that binds to dying and dead cells and activates a process that clears them. Chronically elevated blood CRP levels are associated with increased cardiovascular disease and type II diabetes risks. It also induces IL-6 production by immune cells.
Doctors often include a CRP blood test for complex health problems because it’s a marker of chronic inflammation. At the same time, because obesity is a disease that incurs significant risks of developing other chronic diseases, it's important to maintain a healthy body weight.
What to remember
Inflammation is a vital feature of our immune system. Without it, our body has no mechanism to prevent and fight infection. Inflammation begins with an innate immune response, which is broad and non-specific. It localises and limits the threat, but may not be strong enough to clear an infection.
Meanwhile, highly specific adaptive immunity “studies” the infectious organism and mounts a potent response that’s strong enough to deal with most threats. Furthermore, it can “memorise” the offender, which leads to a quicker and stronger response if the infection dares to try again!
Unfortunately, our strong guardian can be misguided. When inflammation is triggered by a non-infectious stimulus, like atherosclerotic plaque, it is called sterile. There are many potential causes of low-grade sterile inflammation. If the stimulus cannot be removed, the immune response becomes chronic and can persist for decades.
Atherosclerosis and obesity are important factors in chronic inflammation because arterial plaque and adipose tissue secrete pro-inflammatory signals into the bloodstream. An increased abundance of inflammatory chemicals can accelerate many conditions, increasing risks of developing cancer, type II diabetes, cardiovascular disease, and other chronic preventable diseases.
Trying to lose weight is not the only way you can control your chronic inflammation levels. It is also influenced by our microbiome, lifestyle, and dietary choices. Our next article will expose our pro-inflammatory habits and outline routines that can help in reducing chronic disease risks.
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