Diesel exhaust particles are one of the major components of air pollution. These particles are suspended in the air, and are microscopic — less than one-fifth the thickness of a human hair. As we breathe, they are drawn deep into the lungs. Because diesel-powered engines are everywhere, it is almost impossible to avoid them. People that live and work in urban and industrial areas are more likely to be exposed. Combined results from many epidemiological, clinical, and toxicological studies show that diesel exhaust particles are associated with respiratory disorders, as for example severe asthma.
It is not surprising that children are especially susceptible to the effects of these particles. Results form a recenty study entitled “Diesel exhaust particle induction of IL-17A contributes to severe asthma” and published onine (September 23, 2013) in the Journal of Allergy and Clinical Immunology, show that exposure to diesel exhaust particles from traffic pollution leads to increased asthma severity in children.
The study was conducted by researchers at Cincinnati Children’s Hospital Medical Center. and provides insight into the mechanisms responsible for the development of severe asthma in children exposed to high levels of diesel exhaust particles — these mechanisms involve expansion of a type of white blood cells called T helper 17 cells and increased production by these cells of a protein, IL-17A. This protein is known to be associated with several chronic inflammatory diseases, including rheumatoid arthritis, psoriasis and multiple sclerosis.
The researchers studied 235 children and teens with asthma by estimating their diesel exposure attributable to traffic based on where they lived. The researchers also studied mice exposed to diesel particles and dust mites, a common household allergen.
In children with asthma, diesel exposure was associated with more frequent asthma symptoms and increased IL-17A blood levels. In mice, exposure to diesel and dust mites resulted in more severe asthma when compared to dust mite exposure alone. Neutralization of IL-17A in mice resulted in alleviation of airway inflammation induced by diesel exposure.
Gurjit Khurana Hershey, MD, PhD, director of asthma research at Cincinnati Children’s and senior author of the study says that neutralization of IL-17A “may be a useful potential therapeutic strategy to counteract the asthma-promoting effects of traffic-related air pollution, especially in highly exposed, severe allergic asthmatics.”
In addition to children being more susceptible to asthma due to developing lungs, obese children are also more prone to developing asthma. So I was wondering if also obese children are exhibiting an increase in IL-17 in response to T-Helper cells, and according to the study done by Winer et. al, which determined that obesity can also play a role in an increased IL-17 production. So, if therapy suggests neutralization of IL-17 will help with the likelihood of children developing asthma, but would this therapy also work with obese children? Or would there need to be a different approach for these kinds of children because their body could be producing IL-17 without the help of diesel exhaust particles? So maybe an alternative treatment could be used to determine if the use of toll like agonists could be used. Toll-like agonists were employed in a study completed by Aryan et. al, and in this study the toll-like agonists are used because toll like receptors are one of the first defense mechanisms the human body uses in response to an infection and recent studies also suggest that these receptors are used to reduce the likelihood of an airway inflammation.
That is a very interesting suggestion. For another possible solution, I wanted to look at how the T-helper cells were being suppressed to lead to the respiratory disorder. I was looking at a study by Dr. Gurjit Hershey et al. about a genetic region in the T regulatory cells called forkhead box protein 3(FOXP3). Hypermethylation of this region was related to the suppression of T regulatory function. Without this function, there is high response to the diesels particles which lead to severe respiratory disorders. It would seem that the key to this puzzle is the FOXP3. Unless we can control the amount of exhaust fumes in the air, the possible solution to this problem is a type of immunogenetic therapy that can help control the methylation of FOXP3 so the immune response would not be so great in children and so the children can have a healthy respiratory and immune systems.
You’ve brought up an interesting point pertaining to obese children. The correlation between asthma and obesity in children is suggested to come from inflammation caused by body fat, which increases the risk of asthma. If children are prone to having both of these conditions there’s more of a production of IL-17A in the lungs. The suggestion of Toll-like receptors, I think its essential because it can help manipulate the immune response by using the toll-like receptors for therapeutic value.
I had heard of asthma before but I did not recognize that high levels of IL-17A in blood provide negative effect to asthma until reading blog post. It can be understandable because IL-17A is usually associated with allergic responses. Then, how do high levels of IL-17A in blood provide negative effects in asthma?
The article “Interleukin-17 is a negative regulator of established allergic asthma” (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118159/) suggests that IL-17A establish asthma when it regulate negatively. IL-17A reduces lymphocyte and eosinophil recruitment because they regulate productions of Th2 lymphocyte-attracting chemokine (TARC), eosinophil-attracting chemokine eotaxin (CCL 11), and IL-5. Through the experimental neutralization or gene deficient mice, they prove that inhibition of these chemokines is the causes of reduction of allergic asthma. Although It requires for allergic response, It can establish asthma if it is uncontrolled.
It’s no surprise that exposure to diesel exhaust particles causes respiratory problems such as asthma. It also increases hospital admissions and mortality rates in people with chronic pulmonary disease. According to a study, daily exposure to diesel exhaust particles alters the function and amount of macrophages in the lung. The toxic particles lessened CXCL8 cytokine responses to LPS and heat killed E.coli by altering gene expression. Another study demonstrated that exposure to diesel exhaust particles caused major maternal hormone changes in pregnant rats that increased the risk of spontaneous abortion.
There are many other studies that prove the dangers associated with diesel exhaust particles and unfortunately, we are exposed to it everyday. I believe more funding needs to go towards developing alternative fuels.
These are the articles I referred to in my response:
Pollution has been a major problem for centuries, and it has not gotten any better. Diesel has been used to power many means of transportation such as boats and trucks, but now that we know the particles adverse effects, going green, recycling, and finding safer alternative power is as important as ever. The prevention of exposing these diesel particles as well as other forms of pollution may also be as significant as counteracting the asthma. If we can reduce the risk factors and implement the neutralizing therapy to confront the pathogen, we can greatly reduce the number of people that suffers from asthma. With this, I started to wonder what other things scientists are trying to do to help in this fight. Researchers are currently developing drugs to directly attack the protein, IL-17A. Moreover, they have found the vitamin D3 is able to inhibit the production of IL-17. All of these things can help reduce inflammation caused by this protein ad it also give some options for patients in case they are allergic to certain drugs.
It’s interesting that you mention vitamin D3 as a form of therapy. Studies have found that vitamin D deficiency is linked to worse asthma control and increased airway reactivity. Those who are obese are at risk for vitamin D deficiency and also developing asthma. Vitamin D supplementation may improve asthma control by blocking inflammation-causing proteins like IL-17A and increasing production of anti-inflammatory protein, IL-10. More research should be done to see if vitamin D supplementation should be used to treat and prevent asthma.
There are different types of asthma that occur in both children and adults. These can be either child-onset, adult-onset, exercise/cough induced, and several others (MNT). There can be different levels of exposure to diesel particles. So would this, in turn, affect the severeness of the asthma in the child or whether it contributes to asthma in adulthood? Today in the United States, we aren’t exposed to as many industrial environments as other third-world or developing countries. Different pollutants in the air caused by industrial factories in urban and industrial areas, even the United States can contribute to numerous respiratory diseases. It is known that air pollution is a contributor to lung cancer, so if a child is exposed to a large number of diesel exhaust particles and develops asthma at a young age, they may be at an increased risk for lung cancer as an adult. In the article titled “Lung cancer and air pollution”, it was stated that 30-50% of increases lung cancer rates are related to particles that are inhaled from the air. Therefore, not only diesel exhaust particles put a child at risk for asthma, but they may also increase the risk of the child developing lung cancer in the future.
This is a very intriguing point that you brought up. Many people associate tobacco usage with lung cancer but there has been little focus on the consequences of air pollution. In my opinion, I believe that diesel exhaust is a carcinogen. However, I would like to emphasize that there are other contributing factors that may increase that possibility of an individual getting lung cancer due diesel exhaust exposure. A recent study called “Lung Cancer Incidence and Long-Term Exposure to Air pollution from Traffic” showed that individuals that have a low intake of fruits had a higher risk of developing lung cancer when exposed to air pollution. It was determined that fruits contain enzymes that provide protection against oxidative damage to DNA as well as oxidants and prooxidants present in air pollution. Thus, it reduces the formation of DNA adducts.
This article was very informative. I myself have asthma and I had no idea that interleukin 17 played such a role in airway inflammation. However, cystic fibrosis is commonly misdiagnosed as asthma due to its similarities. So are the same mechanisms in terms of increase production of IL- 17 due to T helper 17 cells seen in cystic fibrosis as well? During my search for this answer, I discovered an article called “Is cystic fibrosis a TH17 disease?”. According to this article, it showed that IL-17A is elevated in the sputum of cystic fibrosis patients as well as IL-23 during pulmonary inflammation. This results in neutrophil recruitment and cartilage destruction that is present in IL-17 mediated responses. This confirms that cystic fibrosis is a TH17 disease. I hope future research of neutralizing IL-17A therapy will also be tested on cystic fibrosis patients to help relieve symptoms of lung inflammation.
The insight that diesel exhaust particle exposure causes asthma in children is not surprising as air pollutants have been shown to cause chronic respiratory disorders in children and adults. The awareness that these particles cause respiratory disorders begs the question- What are other effects of diesel exhaust particle exposure on children? I read two articles which collectively show a correlation and causation of diesel exhaust particles to neurological degeneration in mice and children. The article, ” Nanometer size diesel exhaust particles are selectively toxic to dopaminergic neurons: the role of microglia, phagocytosis, and NADPH oxidase.” showed neuron death in mice while the article, ” Early Alzheimer’s and Parkinson’s disease pathology in urban children: Friend versus Foe responses–it is time to face the evidence.” showed neuron death in children. Intrinsically, both studies showed that diesel exhaust particles causes oxidative stress, inflammation, and neuron death in mice and children. Diesel exhaust particles cause respiratory disorders and neurological disease in children. Attached below are the websites whereof the articles mentioned in this post reside.
It’s very obvious that diesel fuel exhaust can be dangerous for anyone who inhales it, especially children. Children’s bodily systems are not fully developed and can’t handle such strong chemicals coming from the diesel fuel exhaust, so it’s not surprising that inhaling such particles can disrupt the function of the developing lungs and cause chronic asthma. Knowing the strength of diesel fuel exhaust, is that the only function of the body system that is disrupts in children? It is also shown that the IL-17A found in diesel fuel exhaust can cause psoriatic arthritis. So not only can diesel exhaust affect the respiratory system, it can travel in the body and affect many other bodily functions.
I knew that the air pollution is becoming big issue today by causing respiratory problems for human bodies. However, I did not understand that IL-17A is a marker for asthma. If person’s high levels of cytokines like IL-17A indicate that he or she has the asthma, we can use CD4+ T effector lymphocytes which are distinguishable in different subsets on the basis of their patterns of cytokine secretion.
Also the activation of Th2 cells during our immune response to asthma can be used as therapy according to the ‘Asthma: new developments in cytokine regulation’ (http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1809003/). This research says that we can develop therapies for asthma by regulating cytokines. IL-17A, IL-4, and IL-13 are secreted from the natural killer cells and these make activation of Th2 for causing AHR.
Therefore, Th2 cells in the lung which are activated for the development of asthma underlying regulators of cytokines transcription which can be key role in therapy.