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Anthropogens: Inducers of Chronic Inflammation and Degenerative Diseases

By Roberta Attanasio

Injuries and infections are facts of life, and we need to deal with them. Thus, it’s not surprising we have developed efficient and magnificent sets of mechanisms that defend us from whatever is perceived as a danger, for example micro-organisms and irritant substances. Inflammation (or inflammatory response) is one of these sets of mechanisms, and not only — inflammation is our first line of defense, as well as the process that leads to repair of the damaged tissue. When the need arises, the inflammatory response stages a battle that results in the classical four signs of inflammation — swelling, redness, heat and pain — with the final goal of eliminating the threat and bring us back to health.

The classical four signs of inflammation result from the coordinated action of different types of white blood cells, mostly macrophages, monocytes and neutrophils. These cells communicate with each other, and with the surrounding cells and tissues, through messenger molecules called cytokines and chemokines. Cytokines cause the dilation of small blood vessels and changes in their walls — because of these changes, monocytes and neutrophils, as well as proteins and fluid, move from the blood into the damaged tissue, leading to swelling, redness, heat and pain. Macrophages, monocytes and neutrophils help to get rid of any irritant substances and dangerous micro-organisms (pathogens).

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Credit: Malene Thyssen, http://commons.wikimedia.org/wiki/User:Malene, licensed under the Creative Commons Attribution-Share Alike 3.0 Unported license.

The role of inflammation, therefore, is to eliminate whatever represents a danger, limit tissue damage, and finally resolve it. Sometimes, however, inflammation becomes long-lasting (chronic). Chronic inflammation has the opposite effect — instead of resolving tissue damage, it leads to tissue degeneration. Chronic inflammation is low-grade, has systemic rather than local effects and is associated with a decreased metabolic rate. It may lead to the development of degenerative diseases, such as heart disease, obesity, rheumatoid arthitis and cancer, among others. In addition, chronic inflammation is frequently present during the aging process, aggravating degenerative diseases.

Chronic, low-grade inflammation may develop following exposure to inducers called “anthropogens”. Anthropogens include factors related to lyfestyle or behavior encouraged by a man-made environment, as for example poor nutrition, inadequate sleep and lack of excercise. Additional anthropogens are represented by man-made chemicals — for examples environmental pollutants such as endocrine disruptors. The effects of a man-made environment, as is the case of social inequality, are considered anthropogens. Aging is sometime thought of an inducer of inflammation. However, not all anthropogens induce chronic inflammation or deleterious effects in general. Some may actually induce positive effects.

Garry Egger, Professor of Health and Human Sciences at Southern Cross University (Lismore, NSW, Australia), offers new insight into the role that anthropogens play in the development of chronic inflammation. Throughout history, the biggest challenge to human health has been posed by exposure to pathogens and subsequent  progression to infectious diseases. However, we’re now in the presence of an additional, widespread challenge: exposure to anthropogens. Such exposure has occurred since the beginning of the Industrial Revolution and, therefore, only for a relatively brief period of time. The immune system, which orchestrates the inflammatory process, has not had time to develop an appropriate response to the newly introduced anthropogens, and reacts with low-grade inflammation to a not-immediately-life-threatening situation — if exposure to the anthropogen persists, the response may become chronic, thus leading to degenerative diseases, which may be considered modern-time diseases.

Induction of chronic, low-grade inflammation by anthropogens may offer a plausible explanation for the global epidemics of degenerative diseases that our planet is currently experiencing (one example is globesity), and may represent the degenerative disease equivalent of the germ theory of infectious diseases — if this perspective is accepted, it will be possible to design novel strategies for the prevention and the management of modern-time diseases.

21 Comments

  • aa_alidina

    Very interestig comment, i agree with the points you made. Makes me wonder the consequence of the ill choices we make as young adults. I believe as young adults in our 20s we think that none of our action will have future consequence, we think sleep deprivation is just a part of growing up, but we never realize that it might lead to chronic inflammation . As your comment stated lack of exercise is also a main factor that could lead to some difficult health issues. Lack of exercise is anthropogen that could just be a start of many health isuues such as heart attack, stroke, kidney probelms, artheritis and many more. Just by walking around for 20 minutes a day we might be able to avoid most our health issues.
    Articles nicely states that we need to be careful about the choices we make that could lead to chornic inflammation. We are soo very afraid of catching influenze or different viruses, but we never think twice that what we are doing to our body, whether sleep deprevation, lack or exercise or choice to eat unhealthy foods can give us much worse health issues.

    • MeganNWynegar88

      I think you are right about most younger people not really considering what they are doing to their bodies or just accepting that lack of exercise, poor diet, and sleep deprivation are just part of life at that age. The point I find more striking, though, is that people in general seem to worry more about microbes than environmental factors. It raises the question whether we are conditioned to dismiss environmental threats simply because they have not been well characterized until (relative to microbes) very recently or if we are just less likely to actively avoid potential pathogens that do not immediately affect us.

      As with many things, I feel education is a key element to “solving” the problem. If environmental dangers were explained with as much emphasis and weight as microbial infection, perhaps individuals would be more likely to take personal precautions to avoid anthropogens and organizations would be more concerned with reducing the production of them

      • SJ

        MeganNWynegar88:

        I completely agree with you. There is definitely a need for education for young people in order for them to realize the consequences of lack of exercise, sleep deprivation, and poor diet. I think things are moving in the right direction and there has been more emphasis placed of recent on healthier lifestyle habits. But I also think that more can be done especially in certain areas of the United States.

  • SJ

    In addition to sleep deprivation, another aspect that results in chronic inflammation for several Americans is our sedentary lifestyle. Increased sugar consumption associated with the modern diet has been discussed as it relates to diabetes; however, there are also concerns about the amount of exercise most Americans are able to incorporate into their daily lives. It makes me laugh how few treadmills are available in January and how many more become available in the following months as more and more Americans break their cliché New Years resolutions to exercise more. It comes as no surprise that less than 50% of Americans have reported working out at least 30 minutes a day for three days a week.

    Like several other anthropogens, lack of exercise can result in chronic inflammation. As a result, researchers have been focusing more on the treatment potential of exercise for chronically ill patients. In fact, several chronic illnesses result in the most sedentary population. One specific disease that has been linked to an inactive lifestyle is chronic kidney disease (CKD). Smart et. al. found favorable attenuation (reduction) of serum inflammatory markers such as IL-6. These findings were consistent for both strength training as well as aerobic exercise. Research focusing on the efficacy of exercise therapy in chronically ill patients can prove to be of great benefit. It is interesting to see that exercise may work even after chronic inflammation has occurred in the body. Reference: doi:10.4236/ojneph.2013.31005 Published Online March 2013 (http://www.scirp.org/journal/ojneph)

    • aa_alidina

      Very interestig comment, i agree with the points you made. Makes me wonder the consequence of the ill choices we make as young adults. I believe as young adults in our 20s we think that none of our action will have future consequence, we think sleep deprivation is just a part of growing up, but we never realize that it might lead to chronic inflammation . As your comment stated lack of exercise is also a main factor that could lead to some difficult health issues. Lack of exercise is anthropogen that could just be a start of many health isuues such as heart attack, stroke, kidney probelms, artheritis and many more. Just by walking around for 20 minutes a day we might be able to avoid most our health issues.

      Articles nicely states that we need to be careful about the choices we make that could lead to chornic inflammation. We are soo very afraid of catching influenze or different viruses, but we never think twice that what we are doing to our body, whether sleep deprevation, lack or exercise or choice to eat unhealthy foods can give us much worse health issues.

    • Samantha S.

      SJ:

      Your comment regarding a sedentary lifestyle and chronic diseases was very good and present a coo relation that I’ve never thought about. The lack of exercise and increased calorie and fat intake by many Americans has undoubtedly contributed to the severe obesity problem, as well as other chronic illnesses (such as chronic kidney disease as you mentioned in your post).

      In the studies that you referenced, or others you may have read, did you come across any details addressing whether or not exercise alone could be used as a therapeutic option or would it be a combination of exercise and some other agent(s)?

      • CZM15

        SJ, you make great points about the importance of exercise in combating chronic inflammation, and your point towards the end of your post about the ability of exercise to help individuals even after chronic inflammation has occurred. I would also be interested to hear your thoughts regarding Samantha’s question about whether your research showed evidence of studies using exercise as a stand-alone treatment for inflammation, or if you saw it was used in conjunction with other measures.
        In my own research, I came across a study conducted by Dr. Stephen Messier of Wake Forest University that compared patient improvement in individuals suffering from chronic inflammation of the joints, dividing the patients into an exercise group, a diet group, and an exercise and diet group. In this study, the group that experienced the greatest reduction in weight, inflammation and pain was the exercise and diet group. This group also experienced the most improved mobility The diet only group saw greater weight reduction than the exercise only group. Also, in this particular instance, the diet only group experienced a greater reduction in inflammation than the exercise only group. I thought this study was an interesting because it did examine whether diet/exercise were most effective alone or together in reducing a type of chronic inflammation. I am sure results would vary when comparing different types of disorders associated with chronic inflammation.

  • mcotton6

    I found this article to be very relatable due to the fact that anthropogens are a major threat to our immune systems and ever prevalent in developed countries such as America. As an Atlanta native, the first thing that comes to mind when I think of an anthropogen is automobile exhaust. Having an emissions test run on my car once a year has always been the norm, but I never really understood the true importance until reading this article and realizing it could be a major contributor to chronic inflammation and degenerative diseases such as lung cancer and heart disease. It would be interesting to see if an increase in transition from fuel burning to electric cars would have a substantial decrease in chronic inflammation in developed countries.

    • MEE

      I found it interesting to learn about what an anthropogen is. However it is very concerning because there are so many anthropogens and they are a result of human “man-made” development. Car exhaust is a good example. I remember my mom always telling me not to breathe it in because it can cause cancer. After learning about chronic inflammation and how it can lead to degenerative diseases this makes sense. Exposure to these antropogens is relatively new so the immune system hasn’t developed a new response and reacts with low grade inflammation. However, people in cities like New York or people that work in factories, they may be exposed more frequently and see chronic inflammation. At the end of the article, it states chronic inflammation by anthropogens could be an explanation for global epidemics of degenerative diseases. I definitely think this is plausible, but there are so many anthropogens I feel it would be hard to come up with strategies for prevention. Switching to electric cars could help in terms of car emissions, but that is only a small fraction of all the anthropogens that exist. I definitely think it is smart to keep studying anthropogens but I feel a solution to the problem will take more time and evaluation of specific anthropogens.

  • BK12

    Many of us may be students or busy professional with families and several things to juggle, and often it is sleep that we sacrifice. The amount of sleep that we get in today’s time and generation has greatly decreased on average (UCSD Psychiatry). Researchers at the University of Melbourne discovered that critical cytokines have been shown to induce sleep (TNF and IL-1β) during infections and that certain components of the immune system have a circadian rhythm. Similarly their research and others done at the Mayo clinic have shown that sleep helps our immune system replenish critical cytokines (IL-2, IL-6, IL-10 and IL-12) and increase certain T-cell populations to increase immune readiness. This reciprocal relationship between sleep and the immune system is still in development, but stemming from this article more and further research from the Mayo clinic show that lack of sleep can lead to other chronic diseases such as obesity and diabetes, both of which can contribute to chronic inflammation. In essence, we as individuals need to be conscious of small factors that we often take forgranted, such as healthy sleep, a good breakfast, or a walk up the dreaded one flight of stairs. The sum of the parts makes the whole, and if we subtract from small areas of our lives, then we also subtract from being fully whole and healthy. References: doi:10.1038/nri1369 ; Mayo Clinic, UCSD

    • Lorna GM

      This is a very interesting concept and it is true that sometimes its the essential things that are overlooked such as a good nights rest and a healthy meal. This rush in life causes the easily accessible things in life such as a quick, sometimes unhealthy meal or coffee to counter the lack of sleep which are only temporary solutions with harmful long term side effects. On the sleep topic, I did some research on its effect on the immune system because I wanted to find out how and why sleep and the immune system interact and learned that the immune molecules and brain neurochemicals are in contact with each other, inducing sleep during infection. It is a bidirectional interaction where lack of adequate sleep affects the immune systems function while the immune system at work during infection alters sleep patterns. During infection both cytokines and serotonin are elevated. It was also interesting to find out that a lack of sleep increases one’s appetite which in partnership with chronic inflammation due to an over worked immune system leads to obesity. Also those who get less than 6 hours of sleep have a 1.7 chance of becoming diabetic while those who get less than 5 hours have a 2.5 chance compared to those who get 7 hours each night (Imeri & Opp. Nat Rev Neuroscience 2009)
      http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2839418/

    • tha5

      According to the Mayo Clinic, the optimal amount of sleep each night for adults is 7-8 hrs. I am also a student, and I agree that most of us struggle to get that right amount of sleep, but it is important for strengthening our immune system. Sleep is important for our innate and adaptive immune responses. We produce the most pro-inflammatory cytokines during our early night sleep. The slow wave sleep stage is specifically important in forming immunological memory because of the endocrine environment that is present during that time. During slow wave sleep, there is a high level of growth hormone and prolactin but a low level of anti-inflammatory hormones. This endocrine environment is important for the interaction between antigen presenting cells and T cells, helps T cells to move from the blood into infected tissues, and promote the migration of naïve T cells to the lymph nodes. The number of naïve T cells is also at a maximum during that time. Source: doi: 10.1007/s00424-011-1044-0.

  • Lauren Haskins

    Asthma is a worldwide, chronic inflammatory disease. According to the American Academy of Allergy Asthma and Immunology, the percentage of affected individuals is on the rise with 8% of Americans (25 million people) affected in 2009 compared to 7% of Americans (20 million people) in 2001. Asthma strikes both adults and children alike, and this influx in affected individuals is of great concern to physicians and urban health professionals.

    One contributing factor to the severity of asthma is the state of chronic inflammation found in the airways. When an allergen is perceived by the body, following the innate immune response, antigen presenting cells transport the pathogen to the lymph nodes where a major histocompatability complex molecule can present the antigen to helper t cells. An adaptive immune response is activated and a storm of cytokines initiate local inflammation in respiratory tissues. This inflammation can obstruct airways and cause bronchial spasms know as “asthma attacks.”

    Anthropogens are definite contributors to the chronic inflammation suffered by asthma patients, particularly in urban areas. Air pollution acts as an allergen that can stimulate the immune cascade, causing inflammation. Continual exposure to anthropogens can force asthma patients into a cyclical pattern of respiratory inflammation. Attempts to reduce anthopogenic factors should be made to reduce this and other chronic inflammatory conditions.

    • Samantha S.

      Lauren Haskins:
      As an individual once afflicted with severe asthma your post grabbed my attention and you presented some very good information. You stated that “attempts to reduce anthropogenic factors should be made to reduce this (asthma) and other chronic inflammatory conditions.” My question is how??

      My reading and understanding of this article considers anthropogenic factors to be lifestyle and behavioral, as well as man-made chemical factors. It could very well be that man-made chemicals we all take, knowingly or not, have an effect on a subset of the population thereby giving rise to the development of asthma but I don’t think that applies for the majority of those affected. Your post has me pondering on the connection between anthropogens and asthma and how you think their reduction could have a positive effect on those suffering from asthma and those who will develop it.

      • Lauren H.

        Samantha,

        I believe that those living in urban environments are particularly at risk for the development of asthma. Not every asthma patient does live in an urban environment, but the positive correlation between air pollution and asthma prevalence shouldn’t be ignored. Public and environmental health officials play a large role in the fight against air pollution. Two examples that impact levels of air pollution stand out in my mind: transportation and radioactive radon emissions.

        First, our transportation systems are in desperate need of reform. Some cities are doing better than others, but not all cities have the appropriate infrastructure for public transportation. For example, in Atlanta there are both train and bus systems, but they don’t extend into the suburbs. Countless people commute into the city daily with record high commute times. Sitting in idle, vehicle exhaust readily pollutes our air. Perhaps creating greater incentives for ride-share programs and the purchase of low emission vehicles would be a good first step.

        Secondly, many of us unknowingly have pollutants in the air in our homes! Radon gas emissions are toxic and have been linked to both asthma and lung cancer, amongst other life threatening conditions. Awareness is key! Public health officials could do more to educate people about radon gas emissions and encourage radon testing. Measures should be taken to reduce this radioactive gas from our homes.

  • Ivy O

    With the acquisition of more knowledge regarding chronic inflammation and its associated diseases, one of the first thoughts that will occur, other than the what the mechanism of the disease pathway is, will be regarding disease prevention. In particular, cancer can be caused by the progression of acute inflammation to chronic inflammation, and more than one-quarter of cancerous tumors result from this process. In a recent study by Ha-Na Lee, the lab proposed ideas regarding chemoprevention by taking a closer look at what causes affected cells to be more prone to cancer. They believe that these cells are damaged because of an alteration in the interaction of lipids that promote the end of and turn off the inflammatory process (prostaglandins, lipoxins, resolvins, etc.). More research into these processes and their breakdown will allow for better control of the end of the inflammatory process by dosing the cells with additional quantities of these lipids, thus preventing inflammation associated cancer, and perhaps ultimately as a method for controlling this type of cancer, provided adjustments can be made to lengthen the half-life of these lipids. Source: Resolution of inflammation as a novel chemopreventive strategy. Semin Immunopathol (2013) 35:151–161

    • chelton

      After reading this posting, I began thinking about the connection of lipids with the end stages of the inflammatory process and cancer. It prompted a thought about the degenerative disease of obesity and the connection with lipids. The World Health Organization published a study on the phenomenon of globesity, which can be found at the following link. (http://whqlibdoc.who.int/trs/WHO_TRS_916.pdf) In this document, various anthropogens were explored. One of the most interesting was the shift in diet for industrialized AND developing countries. In response to cultural ideals of large animal-product meals as a sign of high social status, people are experiencing high-value protein diets, which also means excessive intakes of lipids. This influx of lipids as a result of globesity could create an internal environment of competition with the various lipids of the body and hinder the end of inflammation. Thus, the inflammatory response becomes chronic and creates deleterious effects.

  • Mahathi Venkat

    Acute inflammatory responses are triggered as a protective mechanism against by tissue injury or pathogen infection. Chronic inflammation, however, can be triggered by cellular stress or dysfunction, primarily mitochondrial dysfunction, circulating blood sugars and other inducers.
    Mitochondrial dysfunction can lead to the production of the inflammosome through the cytoplasmic pattern recognition receptors. The inflammosome production results in the activation of the inflammatory interleukin 1B, which recruits immune system components.
    Circulating blood sugars, such as fructose and glucose, through interactions with proteins or lipids produce advanced glycation end products (AGEs). The AGEs interact with receptors for advanced glycation end products (RAGE) that activates nuclear factor kappa-B (NF-kB). NF-kB is translocated to the nucleus and activates a number of inflammatory genes. AGEs are made in vivo, but can also be found in food cooked at high temperatures, including red meats.
    Other possible inducers of chronic inflammation include uric acid, oxidized lipoproteins and homocysteine. These inducers lead to a perpetual low-level chronic inflammatory state known as para-inflammation. If these inducers were able to be controlled, the levels of chronic inflammation could be modulated in an individual, preventing the multitude of diseases that result from it.

    • Claudette

      To M.V.
      A lot of people read this blog because it makes scientific information accessible to everyone. I suspect you are trying to convey very interesting concepts, but those of us that do not understand molecular biology can’t benefit from what you’re attempting to communicate. I would love to understand what you say, so I was wondering if you would be so kind to write again explaining those interesting things about stress and inflammation.

      • BK12

        I am not M.V.(m.v, feel free to addon) But I will try and clarify what I think he is referring to. Our dietary intake greatly influences what occurs in our bodies, and for people with diabetes, this can be a problem. One problem that diabetics face is not being able to regulate blood glucose levels, often times cells uptake too much glucose( a sugar that we often find in many of our dietary intakes).As a result hyperglycemia (high cell glucose levels) results which effectively stops the cells mitochondria from effectively producing ATP molecules by driving out protons. ATP molecules are vital components of our bodies and serve as the main ‘currency’ for the trillions of reactions that occur in our bodies daily. Build up of protons in our mitochondria results in a cascade of pathogenic mechanisms of which AGEs is one, via build up of reactive oxygen species. Remember, our cells only function at particular pH levels. The build up of protons can cause a very Acidic environment which can break down other bio-molecules and disrupt other reactions or even kill cells.The mitochondria architecture enables it to handle a lower pH across its two membranes, but only to a specific amount. As a conclusion, the buildup of AGEs can cause changes in gene expression that can impact inflammatory responses.

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