Introduction to inflammation
Muhammad Usman Naeem, Abdul Ghani MD
Disease Insights
The term inflammation originates from the Latin word “inflammare,” which translates to “to set on fire” [1]. The term represents heat and redness which an ancient Roman doctor recorded in the first century. Inflammation is a natural process and plays an essential role in processes like infection control and wound healing. Inflammation occurs in response to an illness caused by infection, toxic chemicals, or trauma. The reactions caused by inflammation are a keystone of pathology. For instance, a fever indicates that your body’s inflammatory system is functioning properly when you’re sick. However, chronic inflammation can harm you if it occurs in healthy tissues. Chronic Inflammation is the most common link among almost every disease and the factor that causes the progression of several chronic diseases. Research indicates that most, if not all, diseases start and worsen with inflammation, from lupus to arthritis, allergies to asthma, and hepatitis to cancer. Recent research carried by Mainous shows that 34.6% of U.S. adults have systemic inflammation [2]. Medical conditions that result in inflammation typically have names ending in “-itis.” For instance:- Hepatitis: inflammation of the liver.
- Bronchitis: inflammation of the bronchi.
- Cystitis: inflammation of the bladder
Acute vs Chronic Inflammation (friend or foe)
It is important to understand the difference between acute and chronic inflammation because acute inflammation is the body’s immediate response to injury while chronic inflammation can contribute to diseases. The onset of acute inflammation is rapid and often resolves within a few days. It is characterized by classic signs and symptoms and is primarily characterized by the infiltration of neutrophils and increased blood flow to the affected area due to vasodilation. Chronic inflammation on the other hand has a slow onset and can persist for years. It is characterized by less prominent classical signs and symptoms and is primarily characterized by the infiltration of macrophages and lymphocytes.Causes of Inflammation
Various factors can lead to inflammation. The most common ones are:- Inflammatory foods: For example, red meat, bread and pasta made with white flour, deep fried food, and commercial baked goods such as cookies. These inflammatory foods not only trigger the production of inflammatory cytokines, but they also contribute to weight gain, which leads secretion of adipocytokines from fat tissues.
- Toxic chemicals: For example, cigarette smoke. Smoking damages blood vessels, making them more vulnerable to cardiovascular disease and atherosclerosis. It also increases inflammation and the risk of developing chronic inflammatory diseases like rheumatoid arthritis and multiple sclerosis [3]. Smokers have high levels of CRP.
- Obesity: Visceral fat a type of fat that accumulates in the belly produces proteins that trigger low-level inflammation. This inflammation can be local and deep in the abdomen, affecting the liver, pancreas, and kidneys.
- Insufficient sleep: Insufficient sleep results in alterations to inflammatory cytokines and other biomarkers of inflammation. When the circadian rhythm becomes disrupted due to lack of sleep, immune function, as well as overall bodily function, is also impacted.
- Chronic stress: When our ancestors faced danger, their bodies released hormones to either fight or flee. This “fight or flight” response is great for short-term threats, but ongoing stress from work or home can be harmful, leading to chronic inflammatory conditions like depression, rheumatoid arthritis, inflammatory bowel disease, and CVD.
- Alcohol: Excessive alcohol consumption changes the immune system, leading to increased production of pro-inflammatory cytokines. Many diseases associated with inflammation, such as hypertension (HTN), cancer, dementia, and stroke are linked to heavy drinking.
- Pathogens like bacteria, viruses or fungi.
- External injuries like abrasion or laceration with foreign body.
Diagnosis
Acute inflammation is generally recognizable with symptoms like loss of function, swelling, pain, redness, heat, fatigue, and swelling. Chronic inflammations on the other hand occur silently and don’t cause any symptoms. The silent inflammation can be detected with abnormal CBC results but further testing is carried out to diagnose inflammation. These tests include:- Complete Blood Count (CBC): very abnormal results might indicate inflammation. Further testing like CRP and ANA is done to detect inflammation including rheumatoid arthritis (RA).
- C Reactive Protein (CRP): a protein produced by the liver in response to inflammation. It could be high in both acute and chronic inflammation. On the other hand, a negative CRP doesn’t rule out inflammation. Individuals who have CRP levels higher than 3.0 mg/L tend to be physically inactive, less inclined to maintain a healthy diet, have elevated plasma glucose levels, high blood pressure, obesity, and lower HDL [4].
- Anti-nuclear Antibody (ANA): measures the presence of antibodies in the blood, associated with rheumatologic conditions like lupus and rheumatoid arthritis.
Inflammation and Cardiovascular Disease (CVD).
CDC states that heart disease directly leads to one out of every four deaths, resulting in almost 650,000 lives lost annually [5]. Most people are aware that high blood pressure and high cholesterol are significant risk factors for cardiovascular disease, but not enough attention is given to inflammation. When LDL cholesterol particles infiltrate the innermost layers of the artery walls, inflammatory cells bind to them, starting an inflammatory process. The immune system treats the plaque as foreign and initiates a response to wall off the plaque from the blood flow. Phagocytes rush to gobble up the plaque, leading to a buildup of fat and debris within the artery lining. This causes the artery to narrow, potentially leading to a blockage. If a clot forms, it can trigger a heart attack or stroke, which can be life-threatening [6]. A variation of the CRP test, the high-sensitivity CRP (hs-CRP) commonly used to evaluate increased CVD risk. Elevated levels of hs-CRP in the bloodstream are considered a risk factor for CVD, along with LDL-cholesterol and the extent of metabolic syndrome.Inflammation and Cancer
Research shows that up to 20% of cancers may originate due to inflammation [7]. Patients with high inflammation, face the highest risk of developing lymphoma. Chronic inflammation increases the risk of cancer through various pathways. It damages DNA, leading to mutations that facilitate uncontrolled multiplication of cancer cells. Severe DNA damage triggers an enzyme that not only repairs DNA but also activates the release of pro-inflammatory substances. Chronic inflammation creates an optimal environment for the replication and spread of cancer cells. The inflammatory process generates substances such as cytokines, growth factors, chemokines, and free radicals, which promote the proliferation of cancer cells while inhibiting their death [5]. Moreover, it promotes angiogenesis, the formation of new blood vessels that supply tumors, thus facilitating cancer growth.Inflammation and Type 2 diabetes
Diabetes and obesity often go together also referred to as “diabesity.” Both conditions involve inflammation. Inflammation is a significant trigger that initiates the onset of type 2 diabetes after other predisposing factors are in place, such as an unhealthy diet, excess weight, and lack of physical activity. Diabetes is also linked to a higher risk of developing several types of cancer, including ovarian, lung, breast, pancreas, liver, and bladder cancers. There are a few potential reasons for this correlation. First diabetes and cancer share common risk factors, such as obesity, high-fat diet, aging, and lack of physical activity. Second, the changes associated with diabetes, such as high blood sugar, inflammation, and insulin resistance, may also play a vital role in the proliferation of cancer.Inflammation and obesity
Fat cells are often thought of as inactive storage units for calories, but they are actually metabolically active. Fat cells produce various inflammatory substances such as interleukins and TNF, some of which can disrupt insulin function, including TNF and a compound known as resistin. This is why having an “apple” shape, with excess fat around the waist, is more risky than having a “pear” shape, with extra fat around the hips. However, not all products of fat cells are harmful. For instance, fat cells also produce a compound called adiponectin, which reduces insulin resistance. Unfortunately, the more excess weight you have, especially visceral (belly) fat, the more resistance you produce and the less adiponectin. Excess weight can also lead to fat accumulation in the muscles, liver, and other organs. In the liver, storing excess fat can cause inflammation and lead to non-alcoholic fatty liver disease (NAFLD), which is becoming the leading cause of liver and cirrhosis [8].Inflammation and aging
Aging increases the risk of cancer, and age-related chronic inflammation known as “inflammaging”. As people age, levels of CRP and other inflammatory biomarkers tend to rise. It is thought that the composition of gut microbiota becomes more pro-inflammatory as individuals age, which contributes to systemic chronic inflammation.Preventing inflammation
For centuries over ancestors lived on a simple diet and more physical activity but with the introduction of the Industrial Revolution and processed food, we have been physically inactive and eating more processed food which includes inflammatory chemicals. Making healthy lifestyle choices is the best way to reduce inflammation and the risk of chronic diseases. Although drugs like simvastatin and aspirin can be prescribed to reduce the risk of CVD, these drugs only reduce the risk of stroke or heart attack by 25% [9]. Hence, it is important to adopt an anti-inflammatory Lifestyle which includes:
- Eat healthy: Processed foods cause inflammation as they contain omega 6 which is pro inflammatory. Whole foods have anti-inflammatory properties. Consume more vegetables, whole grains, fruits, nuts, beans, and fatty fish (Mediterranean diet). Fish contains omega 3s which are anti-inflammatory. Adopting a Mediterranean diet combined with a medium level of physical activity markedly reduces the incidence of high CRP by 72% [10]. Dietary Inflammatory Index (DII) is a useful tool for evaluating the link between diet and inflammation. Another reason to eat healthy to beat inflammation lies inside the gut. The GI bacteria release chemicals that can either promote or reduce inflammation. The composition of the bacteria in the gut and the byproducts they produce change depending on your diet.
- Increase metabolism: Engaging in just 20 minutes of physical activity daily can reduce inflammation. The workout doesn’t have to be intense; even moderate activities like brisk walking can be effective.
- Maintain a healthy weight: Excess weight increases the risk for multiple diseases. CDC notes that a BMI between 18.5 and 24.9 is a healthy body weight range [11]. Maintaining a healthy BMI will reduce inflammation. Avoid nibbling and try closing the kitchen early at night to avoid late night snacking.
- Get enough sleep: Go to sleep at the same time every night and wake up 7 to 9 hours later, at the same time every morning. Create an ideal sleep environment by keeping your room cool, quiet, and dark. Keep cell phones and computers away to avoid the temptation of using them in the middle of the night. Instead of using screens, engage in calming activities before bedtime, such as reading.
- Reduce stress: Through praying and yoga. Increase meaningful social relationships and faith practices.
- Quit tobacco use: Gradually decrease smoking by reducing the number of cigarettes smoked each day. For example, if you smoke 5 cigarettes a day, decrease to 4 a day and then 3. Do it gradually to trick your brain. Get rid of anything that triggers the desire to smoke including, including lighters, cigarettes, and ashtrays.
- Quit Alcohol use: Alcohol not only increases the production of pro-inflammatory chemicals it also prevents fat burning. Just like smoking gradually decrease alcohol intake to trick your brain. Get rid of anything that triggers the desire to drink including social gatherings.
- Add curcumin to your diet: Curcumin exhibits benefit similar to many major pharmaceutical anti-inflammatory drugs and chemotherapy drugs without any side effects. Curcumin helps with conditions like osteoarthritis (OA), diabetes, obesity, cancer, liver disease, and CVD [12].
Citation list
- McDade, T. W. (2023). Three common assumptions about inflammation, aging, and health that are probably wrong. Proceedings of the National Academy of Sciences, 120(51). https://doi.org/10.1073/pnas.2317232120
- Mainous, A. G., Sharma, P., & Jo, A. (2024). Systemic inflammation among adults with diagnosed and undiagnosed cardiometabolic conditions: A potential missed opportunity for cardiovascular disease prevention. Frontiers in Medicine, 10. https://doi.org/10.3389/fmed.2023.1327205
- Ishikawa, Y., & Terao, C. (2020). The impact of cigarette smoking on risk of rheumatoid arthritis: A narrative review. Cells, 9(2), 475. https://doi.org/10.3390/cells9020475
- Ridker, P. M., Buring, J. E., Cook, N. R., & Rifai, N. (2003). C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events. Circulation, 107(3), 391–397. https://doi.org/10.1161/01.cir.0000055014.62083.05
- Watson, S., Shmerling, R. H., Leighton, S., & Linkinhoker, M. (2020). Fighting inflammation: How to stop the damage before it compromises your health. Harvard Health Publishing, in association with Belvoir Media Group, LLC.
- Pai, S., & Weil, A. (2015). An inflammation nation: The definitive 10-step guide to preventing and treating all diseases through diet, lifestyle, and the use of natural anti-inflammatories. RocDoc Publications.
- Singh, N., Baby, D., Rajguru, J., Patil, P., Thakkannavar, S., & Pujari, V. (2019). Inflammation and cancer. Annals of African Medicine, 18(3), 121. https://doi.org/10.4103/aam.aam_56_18
- Fabbrini, E., Sullivan, S., & Klein, S. (2009). Obesity and nonalcoholic fatty liver disease: Biochemical, metabolic, and clinical implications. Hepatology, 51(2), 679–689. https://doi.org/10.1002/hep.23280
- Liu, T., Zuo, R., Wang, J., Huangtao, Z., Wang, B., Sun, L., Wang, S., Li, B., Zhu, Z., & Pan, Y. (2023). Cardiovascular disease preventive effects of aspirin combined with different statins in the United States general population. Scientific Reports, 13(1). https://doi.org/10.1038/s41598-023-31739-w
- Pitsavos, C., Panagiotakos, D. B., Tzima, N., Lentzas, Y., Chrysohoou, C., Das, U. N., & Stefanadis, C. (2007). Diet, exercise, and C- reactive protein levels in people with abdominal obesity: The Attica Epidemiological Study. Angiology, 58(2), 225–233. https://doi.org/10.1177/0003319707300014
- Centers for Disease Control and Prevention. (2022, September 2). Adult BMI calculator. Centers for Disease Control and Prevention. https://www.cdc.gov/healthyweight/assessing/bmi/adult_bmi/english_bmi_
calculator/bmi_calculator.html - Kunnumakkara, A. B., Hegde, M., Parama, D., Girisa, S., Kumar, A., Daimary, U. D., Garodia, P., Yenisetti, S. C., Oommen, O. V., Aggarwal, B. B. (2023). Role of turmeric and curcumin in prevention and treatment of chronic diseases: Lessons learned from clinical trials. ACS Pharmacology Translational Science, 6(4), 447–518. https://doi.org/10.1021/acsptsci.2c00012
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Muhammad Usman Naeem
Muhammad Usman Naeem is a pre-medical student with a Bachelor’s degree in Biomedical Sciences from the University of South Florida. His primary interests are in neuro-oncology and preventive medicine. Muhammad is actively researching the role of MR1 - Major Histocompatibility Complex Class I-related gene in cancer immunotherapy. Additionally, he has experience working with elderly patients, managing a range of chronic diseases including diabetes, hypertension, and cardiovascular disease.