Steroid Side-Effects & Seven-Fold Suicide Risk

Steroids are used to treat a variety of conditions such as rheumatoid arthritis, systemic lupus erththematosus (lupus), myositis (inflammation of the muscles) and vasculitis (inflammation of the blood vessels).  They work by decreasing inflammation and reducing the activity of the immune system, thereby minimizing  tissue damage and organ failure.  At times they can be life-saving.

However, they are always prescribed with caution due to the long list of well-documented physical side-effects such as:

In addition, steroids are known to cause psychological problems such as sudden mood swings, nervousness, restlessness, and depression.

Now a new study reveals another worrisome side-effect.  According to a group of French researchers, patients prescribed oral steroids are nearly seven times more likely to commit or attempt suicide.

In the largest study of its kind, researchers followed 372,696 adult patients treated with oral steroids between 1980 and 2008 and compared them to patients with similar conditions who were not prescribed steroids.

The results of the study were published last month in the American Journal of Psychiatry. They showed that patients taking oral steroids were seven times more likely to commit or attempt suicide compared with those with the same underlying medical disease not treated with oral steroids.

The steroid treated group was also twice as likely to suffer from depression and more than four times as likely to suffer mania.

The authors of the study concluded primary care physicians should educate patients and monitor oral steroids closely. Lead author Dr Laurence Fardet, a consultant in internal medicine at Saint-Antoine Hospital, Paris, called for caution in prescribing oral steroids: “Where it is essential to prescribe a glucocorticoid, patients and their families should be informed about the possibility of these severe adverse events.”

Have you or your loved ones suffered physical or psychological side-effects from oral steroids? Share your stories with us.

Unlocking the Mystery of Autoimmune Disease

A key feature of the immune system is its ability to discriminate between self and non-self.

When the mechanisms that prevent the immune system from attacking itself break down, it can result in autoimmune disorders such as multiple sclerosis, rheumatoid arthritis, Crohn’s disease and diabetes.

Now researchers at Columbia University Medical Center claim they have not only found out why people with autoimmune diseases attack their own tissues and organs, but also how to correct the problem.

According to a study just published in The Journal of Clinical Investigation scientists have identified a defect in the T cell regulatory pathway which normally controls autoreactive T cells.  The majority of people with Type 1 diabetes who were tested were found to have a defect in CD8+ T cells that impacted their recognition of a common target structure known as HLA-E/Hsp60sp. More importantly, researchers were able to successfully correct the defect in-vitro.

For decades, autoimmune diseases have been treated by reducing overall immune response. That’s been effective in extending life spans, but has been hard on the quality of life for many of those patients,” said lead researcher Hong Jiang, M.D. Ph.D.

Current therapies for treating autoimmune disease include steroids, which systemically suppress the immune system, resulting in multiple side effects, including weight gain and increased susceptibility to infections.  Therapies based on this new research are designed to selectively suppress immune responses to self-antigens without damaging the body’s normal anti-infection and anti-tumor responses.

This research is significant. The Columbia University scientists believe that this greater understanding of the defect could eventually lead to prevention of autoimmune diseases altogether.

SRxA’s Word on Health is keeping everything crossed.

Pac-Man Physiology

Yes, I admit it.  This Word on Health blogger has probably been spending way too much time recently think about blood cells. In the last week alone I have been re-learning basic anatomy and physiology as part of my paramedic course, providing training on infection control and cellular immunity to new emergency services recruits and preparing presentations on blood and coagulation disorders for one of our favorite clients.

So, it’s probably not altogether surprising that a news story about the expanded role of macrophages caught my eye.

For most of our readers, I suspect that the term “macrophage” conjures images of a hungry white blood cell gobbling invading bacteria, in a manner reminiscent of  the 1980’s iconic Pac-man.

It emerges however, that macrophages do much more than that.  Not only do they act as antimicrobial warriors, they also play critical roles in immune regulation and wound-healing.   Additionally, they can respond to a variety of cellular signals and change their physiology in response to local cues.

There has been a huge outpouring of research about host defense that has overshadowed the many diverse activities that these cells do all the time,” said Dr. David Mosser, Professor of Cell Biology and Molecular Genetics at the University of Maryland.  “We’d like to dispel the narrow notion most people have that macrophages’ only role is defense, and expand it to include their role in homeostasis.”

So what are macrophages?  Well, they exist in nearly all tissues and are produced when specialized white blood cells called monocytes leave the blood and differentiate in a tissue-specific manner. The type of macrophage that results from monocyte differentiation depends on the type(s) of cytokines that these cells encounter on their journey. Cytokines, for those not in the know, are proteins produced by immune cells that can influence cell behavior and affect interactions between cells.

For example, macrophages that battle microbial invaders appear in response to interferon-γ, a cytokine that is produced during a cellular immune response involving helper T-cells and the factors they produce. These macrophages are considered to be “classically activated.”

However, when monocytes differentiate in response to stimuli such as prostaglandins or glucocorticoids, the resulting macrophages will assume a “regulatory” phenotype.

Alternately, wound-healing macrophages arise when monocytes differentiate in response to interleukin-4, a cytokine which is released during tissue injury.

According to Dr. Mosser, macrophages can change their physiology and switch types. For example, in healthy, non-obese people, macrophages in fat tend to function as wound-healing macrophages. They are also thought to maintain insulin sensitivity in adipose cells. However, should an individual become obese, macrophages in fat will instead promote inflammation and cause the adipose cells to become resistant to insulin.  Similarly, immune-regulating macrophages produce high levels of the cytokine interleukin-10, which helps suppress the body’s immune response. Suppressing an immune response may seem counter-intuitive, but in the later stages of immunity it comes in handy because it limits inflammation.

According to Mosser, immune-regulating macrophages may hold the key to developing treatments for autoimmune diseases such as multiple sclerosis or rheumatoid arthritis. The focus of new research is on reprogramming the macrophages to assume a regulatory phenotype and prevent autoimmunity.

It might be possible to manipulate macrophages to make better vaccines, prevent immunosuppression, or develop novel therapeutics that promote anti-inflammatory immune responses.”

All of which kind of leads me back to the Pac-man analogy. In the video arcade game, when all the initial dots are eaten, Pac-Man is taken to the next stage where he gets to take on other enemies.   Here, despite the seemingly random nature of the enemies movements, they are in fact strictly deterministic.  Exactly, the same it seems, as it is with macrophages.

Suddenly learning Anatomy and Physiology may get a whole load more interesting for those back-to-school teens!

Alzheimer’s Disease could be reversed by rheumatoid arthritis protein

SRxA’s Word on Health is encouraged to learn that scientists have discovered that a chemical normally produced by the body to fight arthritis, could also reverse the memory loss associated with Alzheimer’s Disease.

Although it’s already known that people with rheumatoid arthritis, have a reduced risk of Alzheimer’s, until recently, most experts assumed this was due to the anti-inflammatory drugs given to treat the disease.

Now, researchers at the University of South Florida have found that a protein, triggered by rheumatoid arthritis, can undo the ‘tangles‘ in the brain that are thought to cause Alzheimer’s.

While people with rheumatoid arthritis are subjected to swollen joints and decreased mobility, the protein produced by the disease stimulates scavenger cells in the body.

The new study, published online in the Journal of Alzheimer’s Disease, found that the protein, GM-CSF, could both reverse the memory loss associated with Alzheimer’s and lower the risk of getting the illness.  In some cases the memory impairment was completely undone after treatment.

The placebo-controlled tests in mice, showed that those treated with GM-CSF had >50% decrease in beta amyloid, the hallmark substance of Alzheimer’s disease. They also showed more microglia – specialized immune cells which remove toxic substances, in the treated animals. In contrast Alzheimer’s mice injected with the placebo salt solution continued to do badly in the tests.

We were pretty amazed that the treatment completely reversed cognitive impairment in 20 days,” said Dr Tim Boyd, the scientist who led the study.

What makes these results especially noteworthy is that the protein is not experimental.  A synthetic form of this naturally occurring protein is already commercially available under the brand name Leukine (sargramostim).  Leukine is a recombinant human granulocyte-macrophage colony-stimulating factor (rhu GM-CSF) manufactured by Genzyme.  While not indicated for use in Alzheimer’s, it has been approved by the FDA to reduce the incidence of severe and life-threatening infections in some chemotherapy patients with acute myelogenous leukemia (AML). Leukine is also used in multiple stem cell transplantation settings.

Our study, along with the drugs track record for safety, suggests Leukine should be tested in humans as a potential treatment for Alzheimer’s disease” commented Prof Huntingdon Potter, a molecular medicine expert involved in the study.

While we recognize that rarely a day goes by without news of some new “breakthrough” for the estimated 35 million people worldwide who suffer from Alzheimer’s disease, your Word on Health team hopes that this latest research brings the promise of a cure or treatment even closer.