UNDERSTANDING INFLAMMATION

Anxiety & Depression Can Be Early Signs

by D U A N E L A W, L. A c. | ( 3 1 0 ) 4 9 8 – 2 7 7 7 

by DUANE LAW, L.Ac. | (310) 498-2777 

Our bodies face constant daily assaults from pathogenic microbes, environmental toxins and industrialized food. The pace of modern life with its non-stop information deluge can push us beyond our limits. A few decades of that wears us out much too soon.

Mammalian bodies need protection. We evolved a complex suite of specialized immune cells and signaling molecules whose sole purpose is to defend and repair our cells and tissues when damage can’t be avoided. These specialized cells:

  • identify and eliminate chemical and biological threats
  • isolate any cells that’ve been damaged beyond repair by those threats,
  • destroy those compromised cells,
  • get rid of the cellular debris that results, and then
  • orchestrate the processes that build new tissue to replace the old.

We call all that inflammation. Life as we know it would not be possible without it.

Think of inflammation as a quiet fire the immune system uses to burn up intruders or damaged cells. That’s actually not far from the truth, because both fire and inflammation involve a chemical process called oxidation.

These inflammatory processes were designed to be temporary. An immune challenge arises, the body deals with it, and then things are supposed to return to normal fairly quickly.

That doesn’t seem to happen today. Many of us are chronically inflamed.

I love this video for the way it brings to life just about all of the gastro-intestinal immune aspects of leaky gut and chronic inflammation.

I do have one beef with it, though. It only mentions the way errant microbes can trigger gut inflammation. It neglects completely the way partially-digested food proteins will do the same thing.

Other than that … gorgeous and informative.

© 2013 Springer Nature Publishing AG. The original can be found online here.

I love this video for the way it brings to life just about all of the gastro-intestinal immune aspects of leaky gut and chronic inflammation.

I do have one beef with it, though. It only mentions the way errant microbes can trigger gut inflammation. It neglects completely the way partially-digested food proteins will do the same thing.

Other than that … gorgeous and informative.

© 2013 Springer Nature Publishing AG. The original can be found online here.

Modern life doesn’t give our immune systems much of a break. Unpredictable combinations of over 85,000 man-made industrial chemicals assault our immune systems daily. Many assume these chemicals have been tested to assess their safety, but the reality is that only a handful have ever been transparently tested for their health effects on humans.1

These chemicals can incorporate themselves directly into our cells and their membranes, altering their activity and their shapes. It’s these changed shapes which alert the immune system that something’s gone wrong, compelling it to react.

These immune challenges come from several different directions:

  • Modern industrialized food can carry the residues of herbicides and pesticides which may have been thought safe for human consumption in trace quantities but which can still kill off friendly bacteria within the gut that help keep inflammation under control.2,3,4,5,6

  • Another factor keeping immune systems aroused: chronic low-grade infections. When immunity isn’t strong enough to eradicate an invading pathogen completely or when the damage it causes can’t be fully repaired, that damage can keep the immune cells permanently activated, creating chronic inflammation.7,8,9
  • The stressful pace of life today also takes its toll.
  • Adrenal glands secrete a substance called Secretory IgA (SIgA) which helps keep gut immunity healthy. Micronutrient deficiencies10 and prolonged stress can both weaken SIgA,11 setting the stage for “leaky gut,” another route to chronic inflammation.
  • These issues are amplified when our diets are full of high-carbohydrate processed foods like the sugars added to so many packaged products, or proteins that are difficult for digestion to process like the gluten in wheat.

B
The innate immune system is like a small town full of gossips.

When a stranger comes to town it’s not long before everyone knows.

The innate immune system is like a small town full of gossips.

When a stranger comes to town it’s not long before everyone knows.

Immunity, Our Modern World and “Sickness Behavior”

We can divide the immune system into two parts. One is called adaptive immunity. Adaptive immune cells are like a smart bomb: created to target and destroy one specific type of invader. This is the part of the immune system vaccinations are intended to train. It can take a week or two for this part of the immune system to gear up to respond in force once it’s been alerted to the presence of an invader. We call that an incubation period.

The other part is called innate immunity. This part of the immune system responds immediately when it detects a pathogen or cell gone rogue. The innate immune system is like a small town full of gossips. When a stranger comes to town it’s not long before everyone knows.

If something stirs up innate immune cells in the gut (for example, like food poisoning) these cells start releasing messenger molecules (cytokines) that tell innate immune cells elsewhere in the body that they need to be prepared to attack. It’s not long before the whole body becomes inflamed.

This is what happens when we catch a flu. The headache, joint pain, fatigue and generally lousy mood we experience in the early stages of a flu are the effect of cytokines activating innate immunity throughout the body.

Again, this system is designed to detect something deserving of attack, destroy it, get rid of the waste and then initiate the process of repair. Before we started living in cities and polluting the biosphere with industrial waste, that system got to do its job from time to time and then take a break until the next toxic or microbial assault.

Not today.

Constant stress, unhealthy diets, chronic infections and toxic exposures can all combine to keep our innate immunity in a continuous state of activation. That’s what keeps us chronically inflamed.

And all that chronic, low-grade inflammation can makes us miserable, triggering pain and setting the stage for all the diseases of aging. For at least ten years it’s been understood that chronic inflammation sets the stage for cardiovascular disease,12,13, cancer,14,15,16 dementia,17,18 neurodegenerative diseases19,20,21 and more.

There’s one more factor to consider. Both innate and adapative immunity work by examining shapes on the surface of every cell and microbe they encounter. If they’ve learned the shapes they detect are characteristic of our own cells or friendly microbes, all is well. But if the shapes they encounter resemble the shapes they’ve learned to associate with invaders deserving destruction, they go on the offensive.

It’s possible for this system to become confused. Sometimes the shapes that trigger immune activity bear an uncanny resemblance to shapes that occur naturally on the surfaces of our own cells.

Then a process called molecular mimicry occurs. When we take into our bodies, for example, proteins that require enzymes humans don’t possess for their full digestion (gluten being a prime example22,23) the protein fragments that result first poke “holes” in the gut lining, allowing the bacteria that live there and protein fragments themselves into the bloodstream. This is another, very powerful way to trigger innate immunity and create still more inflammation.

But innate immunity doesn’t stop there. Remember that very gossipy town? When one set of innate immune cells becomes agitated enough, it’s not long before all of them are agitated, releasing chemical messengers that get the whole system riled up and inflamed.

And if those immune cells are attacking what they think are foreign invaders by targeting specific shapes on the surfaces of those invaders, and if our own body’s cells possess similar shapes, then we’re off to the races with autoimmune disease. Our own immune system starts laying waste to our own tissues and organs.

Hello arthritis, heart attacks and strokes. Hello Alzheimer’s, multiple sclerosis and Parkinson’s.

But long before that … hello anxiety, depression, distractibility. Hello free-floating anger that never quits, looking for a target about which to obsess.

That’s why it’s so important to learn about all this … and then to take action to get inflammation under control.

Constant stress, unhealthy diets, chronic infections and toxic exposures can all combine to keep our innate immunity in a continuous state of activation. That’s what keeps us chronically inflamed.

And all that chronic, low-grade inflammation can makes us miserable, triggering pain and setting the stage for all the diseases of aging. For at least ten years it’s been understood that chronic inflammation sets the stage for cardiovascular disease,12,13, cancer,14,15,16 dementia,17,18 neurodegenerative diseases19,20,21 and more.

There’s one more factor to consider. Both innate and adapative immunity work by examining shapes on the surface of every cell and microbe they encounter. If they’ve learned the shapes they detect are characteristic of our own cells or friendly microbes, all is well. But if the shapes they encounter resemble the shapes they’ve learned to associate with invaders deserving destruction, they go on the offensive.

It’s possible for this system to become confused. Sometimes the shapes that trigger immune activity bear an uncanny resemblance to shapes that occur naturally on the surfaces of our own cells.

Then a process called molecular mimicry occurs. When we take into our bodies, for example, proteins that require enzymes humans don’t possess for their full digestion (gluten being a prime example22,23) the protein fragments that result first poke “holes” in the gut lining, allowing the bacteria that live there and protein fragments themselves into the bloodstream. This is another, very powerful way to trigger innate immunity and create still more inflammation.

But innate immunity doesn’t stop there. Remember that very gossipy town? When one set of innate immune cells becomes agitated enough, it’s not long before all of them are agitated, releasing chemical messengers that get the whole system riled up and inflamed.

And if those immune cells are attacking what they think are foreign invaders by targeting specific shapes on the surfaces of those invaders, and if our own body’s cells possess similar shapes, then we’re off to the races with autoimmune disease. Our own immune system starts laying waste to our own tissues and organs.

Hello arthritis, heart attacks and strokes. Hello Alzheimer’s, multiple sclerosis and Parkinson’s.

But long before that … hello anxiety, depression, distractibility. Hello free-floating anger that never quits, looking for a target about which to obsess.

That’s why it’s so important to learn about all this … and then to take action to get inflammation under control.

As is sometimes the case, the artists were way out in front of the scientists on this one.

It’s all here: a celebration of industrialized food addiction, the alienation, the self-medicating, the anger and rage, the ironic self-awareness and self-acceptance, a fierce insistence on self-determination.

And above all … the rebellious creativity coupled with extreme sensitivity to the zeitgeist that allowed a bunch of intoxicated teenagers to anticipate the connections it would take the next generation of researchers another twenty years to confirm.

© 1993 by Cypress Hill. This can be found online here.

As is sometimes the case, the artists were way out in front of the scientists on this one.

It’s all here: a celebration of industrialized food addiction, the alienation, the self-medicating, the anger and rage, the ironic self-awareness and self-acceptance, a fierce insistence on self-determination.

And above all … the rebellious creativity coupled with extreme sensitivity to the zeitgeist that allowed a bunch of intoxicated teenagers to anticipate the connections it would take the next generation of researchers another twenty years to confirm.

© 1993 by Cypress Hill. This can be found online here.

Inflammation and Mental Health

While not replacing them completely, inflammation-based models of anxiety, depression and a wide range of other psychopathologies are steadily being recognized as superior to the 20th-century’s neurotransmitter-deficiency models.

Which makes sense. After all … even if neurotransmitter deficiencies characterize some cases of anxiety and depression (as would be suggested by substantial, if not universal, clinical experience) … what is it precisely that would be causing these “deficiencies?”

Here’s how it fits together: substantial percentages of the population have genetic SNPs that impair their ability to detoxify (MTHFR and associated methylation cycle SNPs are prime examples.) In pristine environments without substantial toxic background noise, these SNPs were probably adaptive: increasing sensory acuity and other qualities helpful in the hunt.

But today, these same genetic constellations, confronted with a situation for which they were never designed, may become overloaded by the unnaturally high demands placed upon them when exposed chronically to low-level industrial and agricultural chemicals. And because these detox pathways share methyl groups with the pathways that generate neurotransmitters … toxic environments may well be the root cause of at least some “neurotransmitter deficiencies.”

There’s plenty of evidence accumulating that inappropriate immune responses (one way the body deals with those chronic low level exposures) impact mental health.

Cytokines, the chemical messengers that carry the call to inflammatory arms from one part of the immune system to another, rise and fall with feelings of social disconnection and depressed mood.24 We tend to dismiss positive social interactions, and overfocus on the negative when we’re inflamed.25 Not only that, but it’s easy to become addicted to things that inflame us.26

Inflammation is involved in perinatal programming of the developing fetus’ brain in ways that can later contribute to depression, obesity, autism and even schizophrenia.27 Babies of women exposed to air pollution when they were pregnant give birth to children who later express autism at significantly higher rates.28,29,30,31 One study looking into this association documented it in Los Angeles, the town were I was born.32

But while being the child of an inflamed mother may not be the best preparation for life, it’s not only children who suffer. Adults who are inflamed also become depressed, anxious, bipolar or worse.33,34,35

And it’s not just environmental pollution with which we need be concerned. Inflammation can have many sources: chronic infections can cause inflammation contributing to schizophrenia and bipolar features.36

Fortunately … as many different ways as there are to become inflamed … we also have lots of choices regarding what we can all do about the situation.

Here’s some of the best:

  1. Detoxification (to take the load off over-stressed methylation SNPs in the vulnerable,)
  2. Harm reduction strategies like buying indoor air filtering equipment or moving to reduce exposure to air pollutants and other chemicals,
  3. Boosting vitamin D levels, and increasing vitamin C intake, to boost immunity and help the body better control chronic low-grade infections,
  4. Eating organic, to reduce exposure to agricultural toxins that can disturb the microbiome, raising our “inflammatory tone,”
  5. “Eating the rainbow” – a diet rich in colorful fruits and veges supplies a richer mix of the wide range of antioxidants available to us … each of which has its own special role in controlling inflammation
  6. Engaging in therapy to reframe issues and learn new coping strategies, reducing stress that itself increases inflammation,
  7. Somatic therapy forms that reduce stress by leveraging human touch or
    anti-inflammatory endorphin-boosing strategies like exercise (for those who like activity) or
  8. Acupuncture and therapeutic massage (for those who don’t.)

So the good news is that, as many different ways as there are to become inflamed … there’s a wide palette of anti-inflammatory tools at our disposal.

And of course, as in most things functional … the more different strategies we can layer on top of each other, the better things tend to go.

 1. Urbina, I. Think those chemicals have been tested? New York Times: April 13, 2013.

 2. Then C, Bauer-Panskus A. Possible health impacts of Bt toxins and residues from spraying with complementary herbicides in genetically engineered soybeans and risk assessment as performed by the European Food Safety Authority EFSA. 2017. Environ Sci Eur. 29(1):1.

 3. Reuter T, Alexander TW, Martinez TF, McAllister TA. The effect of glyphosate on digestion and horizontal gene transfer during in vitro ruminal fermentation of genetically modified canola. 2007. J Sci Food Agric. 87:2837–2843.

 4. Shehata AA, Schrödl W, Aldin AA, Hafez HM, Krüger M. The effect of glyphosate on potential pathogens and beneficial members of poultry microbiota in vitro. 2012. Curr Microbiol. 6(4):350–358.

 5. Kau AL, Ahern PP et al. Human nutrition, the gut microbiome and the immune system. 2011. Nature. 474(7351):327-36.

 6. Wu HJ, Wu E. The role of gut microbiota in immune homeostasis and autoimmunity. 2012. Gut Microbes. 3(1):4-14.

 7. Kim EY, Battaile, JT et al. Persistent activation of an innate immune response translates respiratory viral infection into chronic lung disease. 2008. Nat Med. Jun;14(6):633-40.

 8. Karin M, Lawrence T, Nizet V. Innate immunity gone awry: linking microbial infections to chronic inflammation and cancer. 2006. Cell. 124(4):823-35.

 9. Holtzman MJ. Asthma as a chronic disease of the innate and adaptive immune systems responding to viruses and allergens. 2012. J Clin Invest. 122(8):2741-8.

10. Hosomi K, Kunisawa J. The Specific Roles of Vitamins in the Regulation of Immunosurveillance and Maintenance of Immunologic Homeostasis in the Gut. 2017. Immune Netw. (1):13-19.

11. Head KA, Kelly GS. Nutrients and botanicals for treatment of stress: adrenal fatigue, neurotransmitter imbalance, anxiety, and restless sleep. 2009. Altern Med Rev. (2):114-40.

12. Bell SP, Giuseffi JL, Forman DE. Cardiovascular biomarkers and their utility in the older adult. 2012. Curr Cardiovasc Risk Rep. 6(5):397-403.

13. Koenig W. High-sensitivity C-reactive protein and atherosclerotic disease: from improved risk prediction to risk-guided therapy. 2013. Int J Cardiol. 168(6):5126-34.

14. Ramsey ML, Conwell DL, Hart PA. Complications of Chronic Pancreatitis. 2017. Dig Dis Sci. Mar 9. doi: 10.1007/s10620-017-4518-x.

15. Samadi AK, Georgakilas AG, Amedei A., et al. A Multi-targeted Approach to Suppress Tumor-Promoting Inflammation. 2015. Semin Cancer Biol. 35 Suppl: S151–S184.

16. Dawit Kidane, Wook Jin Chae, et al. Interplay between DNA repair and inflammation, and the link to cancer. 2014. Crit Rev Biochem Mol Biol. 49(2): 116–139.

17. Zolezzi JM, Inestrosa NC. Peroxisome proliferator-activated receptors and Alzheimer’s disease: hitting the blood-brain barrier. 2013. Mol Neurobiol. 48(3):438–51.

18. Limor Raz, Janice Knoefel, Kiran Bhaskar. The neuropathology and cerebrovascular mechanisms of dementia. 2016. J Cereb Blood Flow Metab. 36(1): 172–186.

19. Andreasson KI, Bachstetter AD, Colonna M, Ginhoux F, Holmes C, Lamb B, et al. Targeting innate immunity for neurodegenerative disorders of the central nervous system. 2016. J Neurochem. 138(5):653–93.

20. Rodrigo Camara-Lemarroy C, Gonzalez-Moreno EI, et al. Arachidonic Acid Derivatives and Their Role in Peripheral Nerve Degeneration and Regeneration. 2012. ScientificWorldJournal. 2012:168953.

21. DeFrancesco-Lisowitz A, Lindborg JA, et al. The Neuroimmunology of Degeneration and Regeneration in the Peripheral Nervous System. 2015. Neuroscience. 302: 174–203.

22. Shan L, Molberg Ø. Structural basis for gluten intolerance in celiac sprue. 2002. Science. 297(5590):2275-9.

23. Koning F, Gilissen L, Wijmenga C. Gluten: a two-edged sword. Immunopathogenesis of celiac disease. 2005. Springer Semin Immunopathol. (2):217-32.

24. Eisenberger NI, Inagaki TK, Mashal NM, Irwin MR. Inflammation and social experience: an inflammatory challenge induces feelings of social disconnection in addition to depressed mood. Brain Behav Immun. 2010 May;24(4):558-63.

25. Muscatell KA, Moieni M, et al. Exposure to an inflammatory challenge enhances neural sensitivity to negative and positive social feedback. Brain Behav Immun. 2016 Oct;57:21-29.

26. Petrulli JR, Kalish B, et al. Systemic inflammation enhances stimulant-induced striatal dopamine elevation. Transl Psychiatry. 2017 Mar 28;7(3):e1076.

27. Bolton JL, Bilbo SD. Developmental programming of brain and behavior by perinatal diet: focus on inflammatory mechanisms. Dialogues Clin Neurosci. 2014 Sep;16(3):307-20.

28. Volk HE, Hertz-Picciotto I, et al. Residential proximity to freeways and autism in the CHARGE study. Environ Health Perspect. 2011 Jun;119(6):873-7.

29. Volk HE, Lurmann F, et al. Traffic-related air pollution, particulate matter, and autism. JAMA Psychiatry. 2013 Jan;70(1):71-7.

30. Kalkbrenner AE, Windham GC, et al. Air Toxics in Relation to Autism Diagnosis, Phenotype, and Severity in a U.S. Family-Based Study. Environ Health Perspect. 2018 Mar 12;126(3):037004

31. Young AM, Chakrabarti B, et al. From molecules to neural morphology: understanding neuroinflammation in autism spectrum condition. Mol Autism. 2016 Jan 20;7:9.

32. Becerra TA, Wilhelm M, et al. Ambient air pollution and autism in Los Angeles county, California. Environ Health Perspect. 2013 Mar;121(3):380-6.

33. Michopoulos V, Powers A, et al. Inflammation in Fear- and Anxiety-Based Disorders: PTSD, GAD, and Beyond. Neuropsychopharmacology. 2017 Jan;42(1):254-270.

34. Felger JC. Imaging the Role of Inflammation in Mood and Anxiety-related Disorders. Curr Neuropharmacol. 2018;16(5):533-558.

35. Howes OD, McCutcheon R. Inflammation and the neural diathesis-stress hypothesis of schizophrenia: a reconceptualization. Transl Psychiatry. 2017 Feb 7;7(2):e1024.

36. Tanaka T, Matsuda T, et al. Infection and inflammation in schizophrenia and bipolar disorder. Neurosci Res. 2017 Feb;115:59-63.

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