K, but what is it actually?
Inflammation is in my top 5 most annoying words. It’s thrown around a lot, but is rarely defined. I see a lot of phrases on the internet like “You need to lower inflammation”, or “You are very inflamed”, or “This supplement lowers inflammation”. But my questions are what, why, and how respectively. If I’m going to be treating something, I want to know exactly what pathways I’m dealing with. I love pathophysiology, or the understanding of how systems work in our bodies, because if I understand how something works I can treat it. There are still a lot of mysteries in medicine, and some parts of inflammation still are, but if we explore what inflammation actually is we can see why a lot of “anti-inflammatory” treatments fail.
So let me take you on a journey through what inflammation actually is.
I think of inflammation as a broad word that describes a biological process with 3 steps: oxidative stress, damage, and clean up. Inflammation and oxidative stress are closely interconnected processes that involve the immune system, particularly white blood cells. White blood cells, also known as leukocytes, play a central role in inflammation and are critical components of the body’s defense against infections and tissue damage.
But first let’s define some important stuff:
- Inflammation: Inflammation is a complex biological response that occurs when the body’s tissues are injured, infected, or irritated by harmful stimuli, such as infections, toxins, oxidative stress, or physical injury. The primary purpose of inflammation is to protect the body from these threats and initiate the healing process. The process of inflammation involves a series of cellular and molecular events that are orchestrated by the immune system. Chronic inflammation is when this process fails to complete fully.
- White Blood Cells and Inflammation: White blood cells are immune cells that travel through the bloodstream and are recruited to the site of inflammation in response to chemical signals released by damaged tissues or invading pathogens. The major types of white blood cells involved in inflammation include neutrophils, monocytes, macrophages, and lymphocytes.
- Oxidative stress or Reactive Oxygen Species: This is easier to think of in terms of chemistry. A byproduct of our cell’s energy making system is an oxygen molecule that isn’t connected to anything, and therefore has an electron hanging out not doing anything. But that’s a really unstable and reactive state to be, so if that reactive oxygen species, or a lone oxygen molecule, isn’t neutralized by an antioxidant (like vitamin C or vitamin E) it can bump into tissues in your body and have a reaction that causes damage. This damage stimulates a response from the white blood cells.
Getting even more specific
- Neutrophils: Neutrophils are a type of white blood cell and the first responders to damage. They are short-lived but highly effective in phagocytosis, the process of engulfing and destroying foreign invaders, cellular debris, and pathogens. Basically they are the first line clean up crew. Neutrophils are also responsible for producing reactive oxygen species (ROS) as part of their defence mechanism. These ROS help to kill and break down the engulfed pathogens. However, excessive ROS production can lead to oxidative stress and potential damage to surrounding healthy tissues. So too many of these, or these cells not being cleaned up quick enough, can start the inflammation process all over again.
- Monocytes and Macrophages: Monocytes, another type of white blood cell, are precursors to macrophages. When they reach the site of inflammation, monocytes can differentiate into macrophages, which are long-lived and highly phagocytic cells. Macrophages play a crucial role in clearing cellular debris and pathogens, and in particular are the clean up crew for neutrophils. Similar to neutrophils, macrophages also produce ROS during phagocytosis, contributing to oxidative stress.
- Lymphocytes: Lymphocytes are a type of white blood cell that includes T cells and B cells. They play a significant role in adaptive immunity, which involves a more specific and targeted response against pathogens rather than other types of damage. Lymphocytes release various cytokines and other molecules that regulate and amplify the inflammatory response. While lymphocytes themselves do not produce ROS, their actions can influence the oxidative stress levels at the site of inflammation.
- Oxidative Stress and Inflammation: Oxidative stress (that isn’t from maladaptive neutrophil and monocyte responses) is a condition that arises when there is an imbalance between the production of reactive oxygen species (ROS) and the body’s ability to counteract or neutralize them with antioxidants. ROS are also weaponized against pathogens but this process can become maladaptive and start harming as much as it helps.
- Inflammatory cytokines are chemicals that are released by the immune system that stimulate more or different immune system responses. The pro-inflammatory cytokines (things like TNF-a, IL-6) are common targets for anti-inflammatory drugs because they stop inflammation from being re-started.
- Resolvins are anti-inflammatory chemicals that are stimulated by white blood cells to start the clean up process. This is where fish oils come in, because fish oils contain the building blocks to make these chemicals. However, drugs like NSAIDs (like ibuprofen) inhibit the production of resolvin molecules. So while these drugs are great for short term pain, chronic use can actually create chronic inflammation. There are also lots of other reasons the clean up process may not go well, and even if the pro-inflammatory side is just way bigger there is only so much the clean up crew can do.
Bringing it all together
So, when there is an excessive and uncontrolled production of ROS or when the body’s antioxidant defences are overwhelmed, oxidative stress can occur. Elevated levels of ROS can lead to damage of lipids, proteins, and DNA, contributing to tissue injury and inflammation. Inflammatory conditions characterized by chronic inflammation can further exacerbate oxidative stress, creating a harmful cycle that perpetuates tissue damage.
To counteract oxidative stress during inflammation, the body relies on antioxidants. Antioxidants are molecules that neutralize ROS, preventing them from causing damage. The body produces its own antioxidants and can also obtain them from dietary sources like vitamins C and E, as well as various plant compounds found in fruits, vegetables, and other foods. So diet is super important, but as I mentioned before, gut issues are really important in inflammation because not only is it a big source of inflammatory chemicals but if you aren’t absorbing anything because your gut is so dysfunctional then the amount of fruits and veggies you eat isn’t as impactful.
In addition, if your body is stuck in the pro-inflammatory/tissue damage pathway, anti-oxidants aren’t going to cut it because it’s targeting the wrong thing. What needs to happen is the unravelling of the immune process. If you see in the infographic above, white blood cells are at the centre of everything.
A lot of natural anti-inflammatories like fish oil and curcumin have pretty mixed results. I think that’s because it’s not looking at the whole picture and addressing the wrong side of the pathway for that person. This inflammatory cycle can be stuck in a few different places and just pushing resolvins really hard isn’t going to do much if you are drowning in neutrophils. It’s also really advantageous to treat where the inflammation is coming from. The most common cause that I see is gut and microbiome issues, but it can also come from diet, insulin issues, toxins, and a poor diet.
This is why I don’t start with the classic anti-inflammatories. Those are usually really great at keeping anti-inflammatory processes going but we need to address the rest of this pathway first before I feel confident those have a chance of working.
Inflammation also comes into a ton of different conditions, and there is a ton of value in treating system inflammation for a lot of people. So if you have any of the following, looking at your inflammatory cascade is probably a good idea.
- Endometriosis
- PCOS
- Any autoimmune disease (like rheumatoid arthritis, lupus, celiac disease, hypothyroidism)
- Joint pain (more relevant for multiple joints than singular joint pain)
- Chronic fatigue
- Eczema or psoriasis
- Concussions or brain fog
- Allergies and asthma
- Fibromyalgia
As a naturopath I’m also really lucky to have some big guns treatments that can usually help get these pathways going pretty quickly, and those are IV antioxidants or ozone. I don’t think they are sustainable long term solutions but they can often go a long way in jump starting these processes.
To sum up, inflammation and oxidative stress are closely linked processes involving white blood cells. White blood cells, particularly neutrophils and macrophages, play crucial roles in the immune response during inflammation. While the controlled production of reactive oxygen species is necessary for pathogen clearance and tissue repair, excessive ROS and oxidative stress can contribute to tissue damage and chronic inflammatory conditions. Inflammation is a complex pathway of events and doesn’t represent a singular thing, so understanding what your inflammation presents at and what part of this pathway needs support is crucial for appropriate treatment.
CD4 T cells: Fates, functions, and faults. Blood. 2008 Sep 1;112(5):1557-69, Zhu J, Paul WE
