Why Inflammation is good and bad…


We read about it all the time, diseases caused by inflammation, auto immune diseases, allergies, ulcers, and a host of other diseases (including mental illnesses) are thought to have the involvement of inflammation in their development!

Well, if inflammation is so bad, if it is involved in the causation of so many illnesses, then why does it exist?

Inflammation in and of it self is not bad. It is a process that our white blood cells carry out to protect our bodies from foreign invaders and repair our bodies after injury. If our immune system didn’t function, we would all have to live in a bubble like the “bubble boy” who had no immune system and therefore could not fight off any infections or repair the smallest of injuries.

When we cut our finger, our white blood cells rush there, an enzyme called Bradykinin actually opens up holes in the blood vessels in the cut’s vicinity so that immune cells can get to the site of the cut!!! Bradykinin binds to mast cells (another of our immune cells) that have just come to the site of infection from the opened blood vessel. It is these mast cells that release the mediators of inflammation such as histamine, heparin, prostaglandins, leukotriene and other compounds. All these molecules are needed in the process of repairing the cut finger. If this process wasn’t functioning well or at all, we would not be able to repair damage to out own bodies.

Also when we have a viral or bacterial infection, our immune system again fights off the virus or bacteria. We have macrophages in our immune cells that will phagocytize (ingest) the bacteria or the cells that have been infected by viruses. Neutrophils and leukocytes are also involved here.

Also the immune system can recognize cancer cells that arise in your body. Yes, the immune system recognizes and destroys cancer cells. But cancer cells are wily, they use cloaking devices to hide from our immune system, so they can establish themselves and grow. But our immune system kills many, many cancer cells before one cell escapes it and becomes a tumor.

So the above is an extremely abbreviated description of what inflammation is and what it does. Inflammation is carried out by our immune cells, which are the armed forces of our body.

It is when these armed forces turn the ammunition against us, rather then against invading bacteria and marauding viruses, that the trouble with inflammation starts.

Take allergies, they happen when your immune system erroneously thinks that, for example, tree pollen is a dangerous invader and reacts against it like it would against Yersinia pestis, the bacteria that causes plague. The tree pollen in and of itself is not a problem, what is a problem is your immune system reacting against it as if it is something dangerous. The runny nose, sneezing, fatigue, sinus headaches/infections are the direct result of your immune system’s mistaken and hypervigilance.

Even more dangerous are the deadly nut allergies so frequently seen these days. For example, peanut allergies. In this, our immune system sees peanuts and thinks danger! All systems go, the production of histamine happens at such a high level that it closes up out breathing passages and throat. This is anaphylaxis. You can’t breathe, and unless you get an epinephrine shot, which will cause vasoconstriction, an elevated heart rate and bring you out of anaphylaxis, you will die! Steroids will also help, but they have to be administered before the anaphylaxis reaction starts.

Now to autoimmune illnesses, here the immune system finds something in your body, such as in your joints in rheumatoid arthritis, that it thinks is foreign. So perhaps a protein in your joints looks like an invader to your immune system, so it unleashes its full deadly response against this protein. The trouble is that it is not an invader, it is a protein in your joint, and your own immune system is destroying your own body! In rheumatoid arthritis it is joints and connective tissue. In Hashimoto’s thyroiditis, your immune system is attacking your thyroid. In autoimmune diabetes, the immune system destroys the beta cells of the pancreas. And there are many, many more autoimmune diseases, where your own body is erroneously attacked by your own immune system.

All the reports I see and post about steroids being able to stop the development of mental illnesses, of the immune system’s involvement in mental illness… who knows, we may ultimately find the immune system is intimately involved in the manifestation, and the development of mental illness.

In summary, inflammation is a critical process that is needed to protect and rebuild from pathological invasion and injury. When this inflammatory response us turned against ourselves, autoimmunity, that is when the trouble starts.

What we have to do is somehow stop our immune system from turning upon our own bodies. Why is it happening more and more these days? Peanut allergies were unheard of not so many years ago! Is it the chemicals with which we douse our food? Chemicals in the air, in our water? If our immune system sees a poison sprayed on an apple as we are eating this apple, and it reacts against the poison in conjunction with the apple, then when we eat only an apple (no poison spray), will our immune system then react to the apple as well? Is that perhaps how all these food allergies started? Possibly. More ideas, more thinking and more research is needed.

“Could Depression Be Caused By An Infection?” I would say Inflammation…

More accurately, could depression be caused by inflammation? People with mental illnesses often experience autoimmune illnesses, meaning their immune systems are over reactive, so much so that they are reacting against their own bodies. I am a case in point, I have food “allergies”, where my immune system reacts to certain foods and then epitopes that look similar to it in my joints and I suffer from joint pain, especially if I eat dairy. Also my thyroid has been knocked out by my own immune system. I have antibodies (autoantibodies) against my own thyroid in my blood, this is called Hashimoto’s thyroiditis. Normally TSH (thyroid stimulating hormone) levels are 0.5 – 4 mIU/L, when I found out that my thyroid had stopped working, my TSH level was 102! Which meant that my pituitary gland kept making TSH to try to make my thyroid work, but unfortunately my thyroid had been disabled by my own immune cells and couldn’t “wake up”! I also have eczema, an autoimmune disease of the skin, thank goodness it’s not too severe. The composer Robert Schumann’s sister suffered from severe eczema and eventually committed suicide. I wonder how much depression played a part in this? I suspect it played a big part.

Another case in point, my mother, who suffered from drug resistant depression with bipolar II, also suffered from rheumatoid arthritis and lupus, both autoimmune illnesses. Same gene pool you say, well look at this article called “Autoimmune Diseases and Severe Infections as Risk Factors for Mood DisordersA Nationwide Study” from: http://archpsyc.jamanetwork.com/article.aspx?articleid=1696348 In this study, Danish researches “found a strong correlation between infection, autoimmune disorders, and mood disorders, strengthening the hypothesis that depression is directly linked to inflammation.” Also from the same study “In a population-based study, Eaton et al found a 70% increased risk of developing bipolar disorder (n = 9920) within 4 years of an autoimmune disease diagnosis and a 20% increased risk in the time span from 5 years onward after the diagnosis compared with the background population.” This pretty significant. Why aren’t drug companies investigating this? A drug that is used widely called Lamictal, a treatment for bipolar II, actually increases the activity of the immune system, making people more prone to “the deadly rash” aka Stevens-Johnson syndrome, an immunologically induced rash which can be deadly if not treated. When I was on it (disastrously, I might add) between 2002 -2008, that was when my joint ache, tendonitis, bursitis problems started. And my mood became worse and worse until I had myself hospitalized at Columbia Presbyterian, and Lithium saved the day!

Moods, autoimmunity and inflammation, definitely related, I actually wrote a long discourse on this very thing in late 2008 in a manic phase, if I can find it and if it makes sense, I will post it here, In the meantime, pharmaceutical companies seriously need to start doing some research on autoimmunity, inflammation and mood disorders. Perhaps an email to my new friends at Astra Zeneca is in order 🙂



Could Depression Be Caused By An Infection?

OCTOBER 25, 2015 6:01 AM ET
Katherine Streeter for NPR

Katherine Streeter for NPR

Sometime around 1907, well before the modern randomized clinical trial was routine, American psychiatrist Henry Cotton began removing decaying teeth from his patients in hopes of curing their mental disorders. If that didn’t work he moved on to more invasive excisions: tonsils, testicles, ovaries and, in some cases, colons.

Cotton was the newly appointed director of the New Jersey State Hospital for the Insane and was acting on a theory proposed by influential Johns Hopkins psychiatrist Adolph Meyer, under whom Cotton had studied, that psychiatric illness is the result of chronic infection. Meyer’s idea was based on observations that patients with high fevers sometimes experience delusions and hallucinations.

Cotton ran with the idea, scalpel in hand.

Pulled Teeth Eliminate Hallucinations

This 1920 newspaper clipping from The Washington Herald highlights Dr. Henry Cotton’s practice of removing infected teeth to treat mental health problems.

A 1920 newspaper clipping from The Washington Herald.

Library of Congress

In 1921 he published a well-received book on the theory called The Defective Delinquent and Insane: the Relation of Focal Infections to Their Causation, Treatment and Prevention. A few years later The New York Times wrote, “eminent physicians and surgeons testified that the New Jersey State Hospital for the Insane was the most progressive institution in the world for the care of the insane, and that the newer method of treating the insane by the removal of focal infection placed the institution in a unique position with respect to hospitals for the mentally ill.” Eventually Cotton opened a hugely successful private practice, catering to the infected molars of Trenton, N.J., high society.

Following his death in 1933, interest in Cotton’s cures waned. His mortality rates hovered at a troubling 45 percent, and in all likelihood his treatments didn’t work. But though his rogue surgeries were dreadfully misguided and disfiguring, a growing body of research suggests that there might be something to his belief that infection – and with it inflammation – is involved in some forms of mental illness.

Symptoms Of Mental And Physical Illness Can Overlap

Late last year Turhan Canli, an associate professor of psychology and radiology at Stony Brook University, published a paper in the journal Biology of Mood and Anxiety Disorders asserting that depression should be thought of as an infectious disease. “Depressed patients act physically sick,” says Canli. “They’re tired, they lose their appetite, they don’t want to get out of bed.” He notes that while Western medicine practitioners tend to focus on the psychological symptoms of depression, in many non-Western cultures patients who would qualify for a depression diagnosis report primarily physical symptoms, in part because of the stigmatization of mental illness.

“The idea that depression is caused simply by changes in serotonin is not panning out. We need to think about other possible causes and treatments for psychiatric disorders,” says Canli.

His assertion that depression results from infection might seem far-fetched, or at least premature, but there are some data to bolster his claim.

Harkening back to Adolph Meyer’s early 20th century theory, Canli notes how certain infections of the brain – perhaps most notably Toxoplasma gondii — can result in emotional disturbances that mimic psychiatric conditions. He also notes that numerous pathogens have been associated with mental illnesses, including Borna disease virus, Epstein-Barr and certain strains of herpes, including varicella zoster, the virus that causes chickenpox and shingles.

Toxoplasma gondii, a parasitic protozoan, afflicts cats and other mammals. Acute toxoplasmosis produces flu-like symptoms and has been linked to behavioral changes in humans.

Toxoplasma gondii, a parasitic protozoan, afflicts cats and other mammals. Acute toxoplasmosis produces flu-like symptoms and has been linked to behavioral changes in humans.

Eye of Science/Science Source

A Danish study published in JAMA Psychiatry in 2013 looked at the medical records of over three million people and found that any history of hospitalization for infection was associated with a 62 percent increased risk of later developing a mood disorder, including depression and bipolar disorder.

Canli believes that pathogens acting directly on the brain may result in psychiatric symptoms; but also that autoimmune activity — or the body’s immune system attacking itself — triggered by infection may also contribute. The Danish study also reported that a past history of an autoimmune disorder increases the risk of a future mood disorder by 45 percent.

Antibodies Provide A Clue

The idea there could be a relationship between the immune system and brain disease isn’t new. Autoantibodies were reported in schizophrenia patients in the 1930s. Subsequent work has detected antibodies to various neurotransmitter receptors in the brains of psychiatric patients, while a number of brain disorders, including multiple sclerosis, are known to involve abnormal immune system activity. Researchers at the University of Virginia recently identified a previously undiscovered network of vessels directly connecting the brain with the immune system; the authors concluded that an interplay between the two could significantly contribute to certain neurologic and psychiatric conditions.

Both infection and autoimmune activity result in inflammation, our body’s response to harmful stimuli, which in part involves a surge in immune system activity. And it’sthought by many in the psychiatric research community that inflammation is somehow involved in depression and perhaps other mental illnesses.

Multiple studies have linked depression with elevated markers of inflammation, including two analyses from 2010 and 2012 that collectively reviewed data from 53 studies, as well as several post-mortem studies. A large body of related research confirms that autoimmune and inflammatory activity in the brain is linked with psychiatric symptoms.

Still, for the most part the research so far finds associations but doesn’t prove cause and effect between inflammation and mental health issues. The apparent links could be a matter of chance or there might be some another factor that hasn’t been identified.

Dr. Roger McIntyre, a professor of psychiatry and pharmacology at the University of Toronto, tells Shots that he believes an upset in the “immune-inflammatory system” is at the core of mental illness and that psychiatric disorders might be an unfortunate cost of our powerful immune defenses. “Throughout evolution our enemy up until vaccines and antibiotics were developed was infection,” he says, “Our immune system evolved to fight infections so we could survive and pass our genes to the next generation. However our immune-inflammatory system doesn’t distinguish between what’s provoking it.” McIntyre explains how stressors of any kind – physical or sexual abuse, sleep deprivation, grief – can activate our immune alarms. “For reasons other than fighting infection our immune-inflammatory response can stay activated for weeks, months or years and result in collateral damage,” he says.

Unlike Canli, McIntyre implicates inflammation in general, not exclusively inflammation caused by infection or direct effects of infection itself, as a major contributor to mental maladies. “It’s unlikely that most people with a mental illness have it as a result of infection,” he says, “But it would be reasonable to hypothesize that a subpopulation of people with depression or bipolar disorder or schizophrenia ended up that way because an infection activated their immune-inflammatory system.” McIntyre says that infection, particularly in the womb, could work in concert with genetics, psychosocial factors and our diet and microbiome to influence immune and inflammatory activity and, in turn, our risk of psychiatric disease.

Trying Drugs Against Inflammation For Mental Illness

The idea that inflammation – whether stirred up by infection or other factors — contributes to or causes mental illness comes with caveats, at least in terms of potential treatments. Trials testing anti-inflammatory drugs have been overall mixed or underwhelming.

A recent meta-analysis reported that supplementing SSRIs like Prozac with regular low-dose aspirin use is associated with a reduced risk of depression and ibuprofen supplementation is linked with lower chances of obtaining psychiatric care. However concomitant treatment with SSRIs and diclofenac or celecoxib – two other anti-inflammatories often used to treat arthritis – was associated with increased risk of needing hospital care due to psychiatric symptoms.

A 2013 study explored the antidepressant potential of Remicade, an drug used in rheumatoid arthritis. Overall, three infusions of the medication were found to be no more effective than a placebo, but patients whose blood had higher levels of an inflammatory marker called C-reactive protein did experience modest benefit.

“The truth of the matter is that there is probably a subset of people who get depressed in response to inflammation,” says lead author Dr. Charles Raison, a psychiatry professor at the University of Arizona. “Maybe their bodies generate more inflammation, or maybe they’re more sensitive to it.”

How infection and other causes of inflammation and overly-aggressive immune activity may contribute to depression and other mental illnesses – and whether or not it’s actually depression driving the inflammation — is still being investigated, and likely will be for some time. But plenty of leading psychiatrists agree that the search for alternative pathologic explanations and treatments for psychiatric disorders is could help jump-start the field.

“I’m not convinced that anti-inflammatory strategies are going to turn out to be the most powerful treatments around,” cautions Raison. “But I think if we really want to understand depression, we definitely have to understand how the immune system talks to the brain. I just don’t think we’ve identified immune-based or anti-inflammatory treatments yet that are going to have big effects in depression.”

But the University of Toronto’s McIntyre has a slightly brighter outlook. “Is depression due to infection, or is it due to something else?” he asks. “The answer is yes and yes. The bottom line is inflammation appears to contribute to depression, and we have interventions to address this.”

McIntyre notes that while the science of psychiatry has a long way to go, and that these interventions haven’t been proved effective, numerous approaches with minimal side effects exist that appear to be generally anti-inflammatory, including exercise, meditation and healthy sleep habits.

He also finds promise in the work of his colleague: “Like most cases in medicine, Charles Raison showed that anti-inflammatory approaches may benefit some people with depression, but not everybody. If you try on your friend’s eyeglasses, chances are they won’t help your vision very much.”

Brain Inflammation triggered by Chronic Pain Linked to Depression and Anxiety


Brain inflammation caused by chronic nerve pain alters activity in regions that regulate mood and motivation. This, for the first time, shows a direct biophysical link exists between long-term pain and the depression, anxiety and substance abuse seen in more than half of these patients.

These findings also point the way to new treatment options for those with chronic pain, the incidence of suicide in patients with chronic pain is second only to those with bipolar d/o. Therefore it would be wonderful to have new treatments.

Researchers found that that pain-derived brain inflammation causes the accelerated growth and activation of immune cells called microglia. These cells trigger chemical signals within neurons that restrict the release of dopamine, a neurotransmitter that helps control the brain’s reward and pleasure centers.

Morphine and its derivatives can be ineffective in treating chronic pain. This study explains why, normally morphine and its derivatives stimulate the release of dopamine, but in rats with chronic pain, administration of morphine does not cause them to produce dopamine, resulting in impaired reward-motivated behavior. However, when these rats are treated with drugs that inhibit microglial activation, they then start producing dopamine.

Next the researchers aim to look at human chronic pain, and determine whether pain derived behaviors might account for mood disorders in these patients.

This can also shed light on mood disorders that are not caused by chronic pain. Of course dopamine is an integral part of the neurotransmitter system that contributes to mood stability. It is also the main neurotransmitter involved in Parkinson’s disease. Hoping for good things to come out of this research.


Article reference below:

Microglia Disrupt Mesolimbic Reward Circuitry in Chronic Pain


Study links brain inflammation triggered by chronic pain to anxiety and depression

Brain inflammation caused by chronic nerve pain alters activity in regions that regulate mood and motivation, suggesting for the first time that a direct biophysical link exists between long-term pain and the depression, anxiety and substance abuse seen in more than half of these patients, University of California (UC), Irvine and UCLA researchers report.

This breakthrough finding also points to new approaches for treating chronic pain, which is second only to bipolar disorder among illness-related causes of suicide. About a quarter of Americans suffer from chronic pain, making it the most common form of enduring illness for those under the age of 60. The Institute of Medicine estimates that this costs our society more than $635 billion per year.

In work with rodents, Catherine Cahill, associate professor of anesthesiology & perioperative care at UCI, Christopher Evans of UCLA’s Brain Research Institute, and colleagues discovered that pain-derived brain inflammation causes the accelerated growth and activation of immune cells called microglia. These cells trigger chemical signals within neurons that restrict the release of dopamine, a neurotransmitter that helps control the brain’s reward and pleasure centers.

The study also reveals why opioid drugs such as morphine can be ineffective against chronic pain. Morphine and its derivatives normally stimulate the release of dopamine. But in research on mice and rats in chronic pain, Cahill and her colleagues learned that these drugs failed to stimulate a dopamine response, resulting in impaired reward-motivated behavior.

Treating these animals in chronic pain with a drug that inhibits microglial activation restored dopamine release and reward-motivated behavior, Cahill said.

‘For over 20 years, scientists have been trying to unlock the mechanisms at work that connect opioid use, pain relief, depression and addiction,’ she added. ‘Our findings represent a paradigm shift which has broad implications that are not restricted to the problem of pain and may translate to other disorders.’

The results of the five-year study appear online in the Journal of Neuroscience.

Next, Cahill and her team aim to establish that pain-derived changes in human brain circuitry can account for mood disorders. “We have a drug compound that has the potential to normalize reward-like behavior,” she said, “and subsequent clinical research could then employ imaging studies to identify how the same disruption in reward circuitry found in rodents occurs in chronic pain patients.”