Inflammation: the fire of the immune system?
June 25, 2020
When we think of inflammation, we usually do so under its original Latin name, inflammare: 'light a fire.' The fire is red and hot, just like the classic signs of inflammation: pain, redness, heat, and swelling.
Inflammation is a defence mechanism by the immune system against foreign invaders, such as viruses or bacteria (pathogens). But, it also helps us to eliminate damaged cells and toxic molecules. It is a repair mechanism for tissue injuries such as incisions in the skin, burns, heart attack, or molecular alterations (e.g. DNA breaks by radiation).
In medicine, inflammation is divided into 'acute' and 'chronic' (if it lasts more than one month) inflammation. The evolutionary function of inflammation in living things should normally be acute: the response of the immune system against pathogens or tissue damage is fast. It aims to minimise the possibility of infection or further injury, contribute to recovering homeostasis and resolve the inflammatory process. However, acute 'uncontrolled' inflammation can become chronic, causing numerous chronic inflammatory diseases, many of which are among the most prevalent in the western world.
Conditions associated with inflammation:
Some examples on conditions associated with inflammation include asthma, chronic peptic ulcer, tuberculosis, rheumatoid arthritis, hepatitis periodontitis, ulcerative colitis, and Crohn's disease.
Also, and perhaps more interesting for prevention, chronic inflammation has been associated with: cancer of various cell types (kidney, prostate, ovary, hepatocellular, pancreatic, colorectal, lung, and mesothelioma), prediabetes and Type 2 diabetes, arteriosclerosis, obesity, neurodegenerative diseases, cognitive decline, and Alzheimer's disease.
Acute inflammation is a short-term process occurring in response to tissue injury, usually appearing within minutes or hours. Inflammation is characterized by five cardinal signs: pain, redness, immobility (loss of function), swelling, and heat. When faced with a stimulus or signal (be it a pathogen, cellular damage, or a chemical compound of its own or that of others), inflammation is the result of the recognition and activation of signalling pathways (NF-κB, MAPK, JAK-STAT) and, finally, the release of 'pro-inflammatory cytokines', such as IL-1β, IL-6, TNF-α, and other pro-inflammatory enzymes and proteins.
Various cells of the immune system (macrophages, monocytes, neutrophils, platelets, etc.) go to the site marked by cytokines as 'pro-inflammatory' to aid in the resolution and repair of damage.
To prevent 'acute' inflammation from becoming 'chronic' inflammation, the inflammatory response must be suppressed once the damage has been repaired. Cytokine gradients should be diluted over time, with the cessation of immune cell recruitment and cell death of the damaged area (apoptosis), recycling, and elimination of immune cells infiltrated into tissues.
When the inflammatory response fails to eliminate tissue damage, the inflammation persists: unfortunately, it's not only external pathogens that can initiate and maintain inflammation. Uncontrolled or dysregulated processes, such as hyperglycemia (high blood sugar) or excess fatty acids (obesity and, above all, visceral adipose tissue), in addition to, of course, alcohol or tobacco, can favour a low-level pro-inflammatory state throughout the body. This type of inflammation is associated with diseases such as Arteriosclerosis, Type 2 diabetes, cancer, and, on the other hand, the accumulation of waste products and premature cellular ageing.
Is it possible to measure inflammation in a blood test?
Medical science has advanced considerably in recent decades, in both the diagnosis and the treatment of inflammatory diseases. There are numerous markers to diagnose and evaluate the response to pharmacological treatment. Some of these markers are exclusive to a single disease, such as rheumatoid factor or citrullinated cyclic peptide antibodies in rheumatoid arthritis, or antinuclear or anti-smooth muscle antibodies in autoimmune hepatitis. Others markers are more general and non-specific, indicating "roughly" the presence (or absence) of inflammation in the body.
Below, we will focus on the non-specific inflammatory markers, offering valuable information that could help us make therapeutic or healthy lifestyle decisions over time.
The best clinical test to confirm chronic inflammation is serum protein electrophoresis, which would show hypoalbuminemia (low albumin) with the polyclonal increase in all gamma globulins (polyclonal gammopathy).
Pro-inflammatory cytokines themselves are detectable, such as factor-alpha (TNF-α), interleukin-1 beta (IL-1beta), interleukin-6 (IL-6), and interleukin-8 (IL-8). The difficulty in evaluating cytokines is that their ranges are not standardized, and the measurement can be expensive, so they are reserved for confirmation of previous diagnostic suspicion.
Finally, we found three relatively accessible markers that indicate systemic inflammation: the highly sensitive C-reactive protein (hsCRP), fibrinogen, and the rate of globular sedimentation (ESR).
High levels of hsCRP would indicate "inflammation" but do not allow differentiation between chronic and acute inflammation since they also rise after recent infections or injuries. Normal serum hsCRP levels are less than 0.55 mg/L in men and less than 1.0 mg/L in women. In the case of fibrinogen, the normal range should be between 200 to 300 mg/dl.
CRP is a protein synthesised by the liver that increases in cases of inflammation. It can be expressed in different ranges, and not always in a standardised way between different laboratories. CRP is expressed in mg/dl (standard CRP) or mg/L (hsCRP, high sensitivity CRP). The distinction between CRP and high sensitivity CRP is only in the unit of measurement (mg/dL or mg/L), detecting lower levels of CRP. Still, it measures the same protein, it is not more sensitive or specific.
ESR is a blood test that measures the speed with which erythrocytes (red blood cells) deposit at the bottom of a test tube. Normally, erythrocytes should deposit relatively slowly; a faster descent would indicate inflammation in the body. ESR is a relatively non-specific and imprecise marker, whose levels increase and decrease more slowly than CRP in case of infection. We often observe increased levels of ESR in arthritis, vasculitis, or inflammatory bowel disease (in addition to infection or cancer). ESR should be evaluated in conjunction with CRP if we suspect chronic inflammation. Normal ESR values are expressed in millimeters/hour (mm/h) (these values may vary depending on the laboratory and the technique used):
Women under the age of 50 should have an ESR of between 0 and 20 mm/h. Men under the age of 50 should have an ESR between 0 and 15 mm/h. Women older than 50 years should have an ESR between 0 and 30 mm/h.
Men over the age of 50 should have an ESR between 0 and 20 mm/h. In the pediatric population, ESR should be between 0 and 10 mm/h.Melio's analysis (https://melio.es/shop) includes two general markers of inflammation: the rate of globular sedimentation (ESR) and the C-reactive protein (CRP).
How to interpret your results?
In the case of active infections or serious tissue damage, the levels will usually be greatly increased (above 10 mg/dL). In this case, the diagnosis must be medical, considering all other signs and symptoms, a detailed medical history and physical examination, and possible additional tests beyond the scope of this article.
However, levels between 0.3 mg dL and 1 mg/dL are considered "slightly elevated" and are observed in cases of type 2 diabetes, hypertension, periodontitis, sedentary lifestyle, smoking, and many other non-inflammatory processes. In general, only levels above 1mg/dL are indicative of significant inflammation or infection. Viral infections can also raise CRP, but usually not to levels as significant as other infectious pathologies.
hsCRP is also used to stratify coronary risk: hs-CRP levels less than 1 mg/dL are considered low-risk arteriosclerotic, levels between 1 mg/dL and 3 mg/dL moderate risk, and levels greater than 3 mg/dL high risk for development of cardiovascular disease.
Importantly, some medications, especially statins (e.g. atorvastatin) and anti-inflammatories (e.g. ibuprofen), falsely decrease CRP levels. Levels can also drop if you take metformin (one of the most common oral antidiabetics), corticosteroids, or specific dietary supplements such as fish oil, lipoic acid, ginger, curcumin, cannabis (and derivatives), hyssop, and Harpagophytum procumbens (harpagophyte), among others.
Also, it should be noted that recent injuries or illnesses can falsely elevate levels, especially if hsCRP is used to stratify coronary risk. Magnesium supplementation can decrease CRP levels.
Clinically, clinicians use CRP to differentiate between chronic inflammation and acute infection, especially in cases of abrupt and significant elevation. However, levels between 1 mg/dL to 10 mg/dL are difficult to interpret, especially if symptoms do not accompany them since pathologies such as rheumatoid arthritis or lupus produce persistent elevations. Levels above 10mg/dL are associated with infection in 80% of cases, while results above "1mg/dL" are considered "suggestive" (although not determining) of "clinically significant inflammation."
And in practice?
At Melio, we consider that to increase our longevity and well-being, we must establish clear objectives and reduce inflammation through lifestyle and nutritional interventions. If our CRP levels elevate above 1mg/dL in the absence of active infection and/or classic autoimmune or inflammatory diseases (such as rheumatoid arthritis, chronic asthma, or Crohn's disease), it may be appropriate to explore whether the cause could lie in our lifestyle choices, and act on them before resorting to pharmacology, unless indicated by your doctor.
The first thing we have to do is take a baseline measurement of the inflammation present in our body. This measurement, under normal conditions, should be carried out in a period during which we have not suffered any infectious disease that could affect the results (or, if possible, any other pathology).
If we suffer from metabolic syndrome or obesity (BMI is correlated with the amount of pro-inflammatory cytokines, as well as visceral obesity), we are smokers, or we follow a "sub-optimal" diet (rich in saturated fat, trans-fatty acids or refined carbohydrates), we frequently experience sleep disorders (insomnia), dysregulation of circadian rhythms or stress (both physical and emotional), we should check our levels of inflammation with, for example, an analysis from Melio.
Do you already know your "basal" levels of inflammation via CRP?
Are they above or below 1mg/dL? If they are above 10mg/dL, you should consult your doctor to investigate other causes of inflammation and to rule out acute bacterial or viral infections.
If they are between 1 and 10mg/dL, you and your doctor must assess the results together, taking into account the possible presence of other concomitant diseases (uncontrolled diabetes, arthritis, and other joint diseases, allergies, etc.) to make a differential diagnosis.
Given that figures in this range are clinically relevant to atherosclerotic risk, surveillance may be prudent. Below 1mg / dL, or around this figure, is where we will have the greatest margin to act. As we have said, levels between 0.3 mg / dL and 1 mg / dL are observed in diabetes, hypertension, periodontitis, smokers, and a sedentary lifestyle.
Our objective will be to introduce changes in lifestyle and nutrition to reach undetectable levels of CRP (the precision of the test may vary between laboratories, so please be conscious of this if you have had tests from other laboratories in the past).
However, at Melio, we are not satisfied with offering generic advice to "lose weight and eat healthier." Below, we offer some specific directions that you could follow.
Losing weight is the most effective way to reduce low-grade inflammation: it is also the most generic recommendation we can make. Weight loss is a relatively slow process and involves numerous changes in our lifestyle, physical activity, and nutrition in the first place. Losing weight is equivalent to creating a caloric deficit or calorie restriction. However, the way to achieve this caloric deficit can be very diverse: moderate constant deficit (for example, "300 kcal" a day below our caloric expenditure, either by reducing intake or increasing activity); or through the practice of alternating intermittent fasting (alternate day fasting), with some days with a higher caloric deficit (for example, "2 days of 1000 kcal deficit", "5 days of normal intake"). If you notice, "300x7 = 2100 kcal", and "1000x2 = 2000 kcal". Weekly weight loss (equivalent to about 250g of "adipose tissue" if we juggle the maths) is the same, but the long-term metabolic repercussions (hormones that increase appetite, decreased basal metabolic rate) are greater in constant restriction, in comparison with "peaks" of caloric deficit (intermittent fasting). If you practice fasting 16: 8 daily (16h fasting, 8h feeding), but consume your maintenance calories, you will not lose weight! Keep this in mind when designing your weight-loss protocol and adjust calories to be calorie deficient, even if you practice intermittent fasting daily.
How does all this translate into practice?
There are numerous procedures to lose weight, but thermodynamically, they always translate into "caloric restriction" (beware of the metabolic repercussions, which can be very different!).
The simplest way to start is to create a caloric deficit in your current diet ("eat less") or increase your physical activity ("move more"). This advice is hazy, imprecise, and almost useless. What you need are two pieces of information: your approximate daily energy expenditure (you can use a calculator for "TDEE" (total daily energy expenditure), which you can find on the internet), and your current weight— nothing else. If your weight has been stable in the last few months, and the figure provided by the calculator is equivalent to your daily intake (approximately!), You already have your "daily caloric expenditure." Now you can reduce some dietary intake during the week or increase your exercise a little to reach the caloric deficit of your choice.
Is weight loss necessary during intermittent fasting? For inflammation, clinical studies are contradictory: we found examples of decreased inflammation markers in clinical trials evaluating "fasting-mimicking diets," but also the absence of significant changes to hs-CRP, TNF -α and IL-6, in others. By contrast, cellular oxidative stress does appear to be reduced even without simultaneous weight loss (caloric deficit).
What if my weight is adequate, or I don't want to lose weight, but still suffer from chronic inflammation?
Implement a strength-training exercise routine and/or cardiovascular training. Regular physical exercise not only helps control and maintain an optimal weight: it produces a clear decrease in inflammatory markers, helps build muscle mass, and decreases your risk of diabetes and cardiovascular disease.
Increase your intake of foods with anti-inflammatory properties (more on these below) and reduce your intake of simple sugars, refined carbohydrates, foods with a high glycemic index, trans and hydrogenated fatty acids. Eat natural, unpackaged foods, with lots of vegetables and fish, like salmon. Examples? Blueberries, brussels sprouts, cabbage, spinach, broccoli, and cauliflower are rich in antioxidants and polyphenols.
Reduce, as far as possible, taking antibiotics (unless, if prescribed by your doctor, it is important to complete the treatment, so always follow your doctor's instructions), antacids and non-steroidal anti-inflammatory drugs (e.g. ibuprofen) due to their negative effect on the intestinal flora, which can damage the intestinal wall and increase chronic inflammation ("leaky gut").
Sleep more, sleep better. Restful sleep (at least 7-8h per night) helps maintain optimal hormone levels for tissue repair. Take care of your sleep hygiene (let's be frank, we know that it is difficult to limit the use of screens before sleeping: try using blue light filters to reduce their impact).
Intake of soluble and insoluble fiber is associated with decreased IL-6 and TNF-α in clinical trials (have we already mentioned that it is good to eat vegetables?). How about replacing the usual meat/fish accompaniments (bread, pasta, rice) with a large portion of grilled vegetables if you want to save time and effort? Give this small change a try, and you will probably also see an improvement in your weight due to unconscious calorie reduction.
What specific foods can help you fight inflammation?
Green and black tea polyphenols are associated with a reduction in CRP. Curcumin produces significant improvements in animal models of inflammatory diseases. A higher intake of omega-3 fatty acids (fish oil) is associated with lower levels of TNF-α, CRP, and IL-6. Magnesium intake and/or supplementation is associated with a significant decrease in hsCRP, IL-6, and TNF-α.
Vitamin D works by indirectly suppressing inflammatory mediators, such as prostaglandins and NF-κB
Vitamin E, zinc, and selenium work as antioxidants in the body.
If you suffer from chronic inflammation, it is best to focus on the large clusters of behavioral changes: improving your diet and exercising correctly and strategically (not necessarily spending more time training, but instead training smarter).
Assuming you have addressed these "big" inflammation triggers: what else can you do to optimize your body's anti-inflammatory capacity? Oxidative stress and inflammation are inversely proportional to longevity (more chronic disease, less quality of life in old age), so any extra steps you can take to reduce chronic inflammation are welcome.
Clinically, regular use of glucosamine, chondroitin, and fish oil (DHEA) supplements are associated with a significant decrease in hsCRP. Vitamin C supplementation can help reduce inflammation and protect against associated cardiovascular risk. Consider consuming or supplementing with mung beans and sesame seeds. As we have already mentioned, curcuminoids and magnesium also reduce CRP, but it is important to look for bioavailable preparations and supplements. Resveratrol, as a concentrated supplement, is an excellent anti-inflammatory, which significantly reduces TNF-α and hs-CRP. The list of antioxidants and anti-inflammatory supplements is long, and its effect in clinical trials is variable and heterogeneous. With a balanced and complete diet, the overuse of antioxidants could even have unwanted effects! If you are considering using any particular anti-inflammatory nutrient, consult the scientific literature on it to ensure that it will provide you with the desired benefits.
Check with your doctor before starting supplement use.
Have you already introduced any of these nutritional changes in your life?
Check its effect after some time (one or two months, or once you can objectively measure, for example, a change in your weight), repeating your Melio analysis (https://melio.es/shop). If you have combined several strategies to reduce inflammation, the effect is likely to be combined and faster. The absence of inflammatory markers in your analysis can assure you that you are taking the right steps. Still, the true benefits will be in your energy levels, vitality, and well-being.
Choose your preferred anti-inflammatory strategy and start reducing your level of inflammation today!
NOTICE: Tis,his informative article is based on the bibliographic sources cited below and has been reviewed by the Melio Reviewers Committee. All content is valid as of the date of publication, but may not include more recent previews. This blog is presented for informational purposes only and does not constitute the practice of Medicine, Nursing or other professional health services, including the provision of medical advice, and therefore does not constitute a doctor-patient relationship. The use of information or materials linked from this blog are under the responsibility of the user. The content of this blog is not intended as a substitute for medical advice, diagnosis or treatment.
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