Tag Archives: Inflammation

Small study showed colchicine improved outcomes in COVID-19 patients

A small randomized, double-blind clinical trial published in RMD Open showed colchicine to be safe and effective in treating moderate to severe COVID-19 infections in hospitalized patients. In the study, patients who took the inexpensive drug required supplemental oxygen and hospitalization for less time. This is the first randomized controlled trial (RCT) on colchicine for COVID-19.

Colchicine is most commonly used to prevent attacks of gout or pseudogout arthritis, which are types of arthritis caused by a buildup of crystals in the joints. Blood cells travel to these areas of inflammation, causing pain and swelling. Colchicine prevents white blood cells from traveling into these areas and therefore helps to reduce pain and tenderness.

Colchicine can also be used to treat acute attacks when nonsteroidal anti-inflammatory drugs (NSAIDs) such as naproxen or ibuprofen cannot be used for safety reasons or have been ineffective. Colchicine is an alkaloid naturally occurring in Colchicum autumnale a plant of Liliaceae family.

Now, it has also been shown to be effective against COVID-19.

From April 11 to August 30, 2020, 72 Brazilian patients received either a placebo or 0.5 milligrams of colchicine three times a day for 5 days followed by the same dose twice a day for 5 days in addition to a standard COVID-19 treatment of azithromycin, hydroxychloroquine, heparin, and (after the RECOVERY Collaborative Group results were announced) glucocorticoid. Methylprednisolone was given if supplemental oxygen was 6 liters per minute or higher.

The most common side effect was diarrhea (16.7%), and colchicine doses were adapted if the patient weighed at least 176 pounds (80 kilograms) or had chronic kidney disease. Those on colchicine needed oxygen for an average of 4 days and stayed in the hospital for an average of 7 days; whereas, the control group needed oxygen for 6.5 days and stayed 9 days. The drug’s effect on ICU admission or mortality rate was not quantified, although the researchers note that 1 patient in the colchicine group went to the ICU compared with 3 in the placebo group. Two patients died in the study, both in the placebo group.

While the researchers acknowledge these results are not yet generalizable (34 of 35 patients receiving colchicine were overweight or obese), they concluded colchicine’s ability to slow systemic inflammation is promising. Systemic inflammation is the hallmark of hospitalized patients due to COVID-19. There is no specific treatment but supportive care and attempts to control the immune activation improve the clinical picture. By diminishing the activation of leucocytes, colchicine may be an intervention worthy of being tested further in more patients.

Age-related cognitive decline reversed in mice by fighting inflammation in the brain

As mammals age, inflammation levels increase. I’m not talking about painful reactions to wound or infection, but rather a more low-key, grinding, background inflammation that grows increasingly intense the longer we live. This growing inflammation has been associated with diabetes, high blood pressure, frailty, cancer, and just about every chronic health problem we tend to see in old age. This also includes cognitive decline and, at least in this case, scientists believe that it can be reversed through managing inflammation in the brain, as studies on mice have shown.

Researchers at the University of Brighton in the UK found that microglia — a specialized population of macrophage-like cells in the central nervous system, which act as immune cells that defend the brain and spinal cord from foreign invaders — are very vulnerable to changes in the levels of inflammation, particularly to a molecule called  prostaglandin E2(PGE2).

When this molecule was in high amounts, the microglia had trouble carrying out their normal cellular processes and related cells didn’t generate energy as well as they could.

Levels of PGE2 naturally increase with age in our cells and those of other mammals due to the growing number of senescent cells. These dysfunctional cells cannot divide anymore and their presence causes the release of PGE2, as well as other inflammatory molecules.

But there’s a way to reverse this process. Writing in the journal Nature, scientists described how PGE2 exerts its effects on cells by interacting with the EP2 receptor on the macrophages, another important type of white blood cell.

When these white blood cells were treated in the lab with drugs that turned this receptor off, the cells recovered. Moving away from the petri dish, the researchers replicated the experiment on mice.

The researchers genetically modified rodents that lacked the EP2 receptor and simply waited for them to grow old (the average lifespan of a mouse kept in captivity is two years). They then tested the cognitive abilities of these elderly mice by subjecting them to a barrage of tests, including navigating mazes and “object location” tasks.

Strikingly, the researchers found that the old genetically modified mice could learn and remember things just as well as their young counterparts. The same effects were replicated in old, normal mice that weren’t genetically modified but which received drugs that turn the EP2 receptor on or off.

Essentially, this series of experiments shows that suppressing the PGE2 receptor may represent an important target for treating and maybe even reversing age-related cognitive disorders. Or at least that seems to be the case in mice. Clinical trials in the future on humans may shed more light.

In the meantime, research has shown that foods such as blueberries, strawberries, and spinach improve cognition in both older mice and people. These foods are rich in fisetin, quercetin, and resveratrol, which are known to flush senescent cells out of the body. One possible mechanism by which they may achieve this is by blocking PGE2 at the cellular level. So until more research can offer more straightforward answers, stock up on that spinach.


Our white blood cells could be ‘reprogrammed’ to lower inflammation on demand

White blood cells receive ‘orders’ from our bodies to cause or subdue inflammation, a new paper reports, as a natural part of the immune response.

A mouse macrophage engulfing two particles at the same time (unrelated to the study).
Image via Wikimedia.

They argue that this effect can be used to prevent Acute Respiratory Distress Syndrome (ARDS), which affects some COVID-19 patients. ARDS is a type of respiratory failure caused by a buildup of fluid in the lungs.

Pimp my immune response

“We found that macrophage programming is driven by more than the immune system — it is also driven by the environment in which the macrophages reside,” said lead author Asrar Malik, the Schweppe Family Distinguished Professor and head of pharmacology and regenerative medicine at the University of Illinois at Chicago (UIC).

Macrophages are those immune cells that find a threat, wrap around it, and start digesting it. However, the new findings showcase that they also play a part in controlling inflammation. While a natural part of our bodies’ efforts against infection, and quite effective against them, excessive or prolonged inflammation can also damage our own tissues and organs.

In essence, these cells both cause and keep inflammation in check. The team analyzed how they determine which of the two approaches they use at any given time using mice. Their goal was to help patients suffering from excessive inflammation and conditions such as ARDS while infected with the coronavirus.

“We demonstrated that lung endothelial cells — which are the cells that line blood vessels — are essential in programming macrophages with potent tissue-reparative and anti-inflammatory functions,” said Dr. Jalees Rehman, UIC professor of medicine and pharmacology and regenerative medicine and co-lead author of the paper.

The researchers found that one protein, R-spondin-3, was present in high levels in the blood during injury and inflammation. The next step was to genetically-engineer lab mice to lack this protein in these cells — which led to the macrophages no longer dampening inflammation.

“Instead, the lungs became more injured,” said Bisheng Zhou, UIC research assistant professor of pharmacology and regenerative medicine and first author of the study. “We tried this in multiple models of inflammatory lung injury and found consistent results, suggesting that blood vessels play an important instructive role in guiding the programming of macrophages.”

The findings point the way towards a promising avenue of treatment for ARDS, but could also help us understand why some patients have better outcomes after a COVID-19 infection than others. Our own immune response has been shown to cause an important part of the damage associated with this disease. Poor vascular health or other underlying conditions that affect our blood vessels could impact our recovery, the team believes.

While the study only worked with lung tissue, it’s likely that those in other organs would show the same mechanisms, according to the authors.

The paper “The angiocrine Rspondin3 instructs interstitial macrophage transition via metabolic–epigenetic reprogramming and resolves inflammatory injury” has been published in the journal Nature Immunology.

Credit: Pixabay.

Negative mood may trigger inflammation in the body

Being sad, angry, or in a negative mood in general, is associated with an immune response that causes inflammation in the body. The findings suggest that inflammation could be used to diagnose the psychological well-being of patients. Conversely, the findings also suggest that therapies targeting an individual’s mood, which is modifiable, could improve poor health.

Credit: Pixabay.

Credit: Pixabay.

Researchers at Penn State measured the mood of 226 adult participants from a housing development in the Bronx, New York. Each participant was asked to recall their feelings over a previous period of time as well as how they were feeling in the moment. These self-assessments were recorded multiple times over a two-week period. Each assessment was followed by blood tests that looked for biomarkers of inflammation.

Inflammation is actually very important to our health. It’s the body’s way of signaling the immune system that it’s time to heal and repair damaged tissue or defend against invaders, such as viruses and bacteria. Without inflammation, wounds would fester and infections could easily kill. But when the signaling persists for too long, chronic inflammation may trigger conditions such as heart disease or stroke, and may also lead to autoimmune disorders, such as rheumatoid arthritis and lupus.

The study’s authors found that negative mood accumulated during the week closer to the blood draw was linked to higher levels of inflammation in the body. What’s more, the correlation between negative mood and inflammation was stronger closer to the blood draw. Conversely, positive mood was associated with lower levels of inflammation.

Unlike previous research efforts, the present study not only used standard questionnaires that gauge a participant’s feelings but also asked them how they felt in the moment.

It’s only recently that scientists have started to include inflammation in theories of depression, so there’s a lot of ground to cover. It could be that negative mood, such as living through a stressful event in one’s life, triggers biological reactions that lead to inflammation. Interestingly, the most widely used therapies for depression have been shown to reduce inflammation. Often times, these therapies involve lifestyle changes, such as exercise and diet.

“We hope that this research will prompt investigators to include momentary measures of stress and affect in research examining inflammation, to replicate the current findings and help characterize the mechanisms underlying associations between affect and inflammation,” principal investigator Jennifer Graham-Engeland, associate professor of biobehavioral health at Penn State, said in a statement.

“Because affect is modifiable, we are excited about these findings and hope that they will spur additional research to understand the connection between affect and inflammation, which in turn may promote novel psychosocial interventions that promote health broadly and help break a cycle that can lead to chronic inflammation, disability, and disease.”

The findings appeared in the journal Brain, Behavior, and Immunity.

woman grief

Widows and widowers who suffer from intense grief risk inflammation that can kill

The grief of losing a life partner can literally kill you. A new study found that people who showed elevated symptoms of grief following their spouse’s death were at risk of inflammation, predisposing them to a heart attack, stroke, and a premature death.

woman grief

Credit: Pixabay.

Researchers at Rice University examined the blood of 99 people whose spouses had recently passed away. They then divided the participants into two groups: those that showed symptoms of elevated grief — not being able to move on, a sense that life is meaningless, inability to accept the reality of loss — and those who didn’t.

The bodily inflammation that widows and widowers in the second group experienced was 17% higher, the authors reported in the journal Psychoneuroendocrinology. Some suffered heavily from their loss, as the researchers found the inflammation levels of people in the top one-third of the elevated grief group was 53.4% higher than the bottom one-third.

Grief sickens

“Previous research has shown that inflammation contributes to almost every disease in older adulthood,” Chris Fagundes, an assistant professor of psychological sciences at Rice University, said in a statement. 

“We also know that depression is linked to higher levels of inflammation, and those who lose a spouse are at considerably higher risk of major depression, heart attack, stroke and premature mortality. However, this is the first study to confirm that grief — regardless of people’s levels of depressive symptoms — can promote inflammation, which in turn can cause negative health outcomes.”

Anecdotally-speaking, most people probably know of some older couple in which, after one of them dies, the spouse ends up dying shortly after, despite having been in relatively good health. There’s actually a lot of science that explains why this happens so often.

A 2014 study published in Ageing and Immunity studied two small groups of mourners, one with an average age of 32 and the other with an average age of 72, and similarly-aged control groups of people who had not recently experienced a loss. It found that elderly widows and widowers had reduced function in their neutrophils — a white blood cell used to fight off infections — compared to the non-bereaved peers, making them more vulnerable to potentially fatal infections. Grief has also been found to aggravate physical pain, increase blood pressure and blood clots, and exacerbate appetite loss, perhaps because grief is known to make people find less pleasure in food.

These new findings suggest that grief has a significant impact on our health, adding to a growing body of evidence that suggests those who have been widowed are at a higher risk of premature mortality. Physicians should identify grief-stricken individuals as being at risk and should devise interventions that target these risk factors, like behavioral therapy or drugs.


Wooden Figure belly ache.

Cannabis does reduce intestinal inflammation, and now we know why

New research on mice shows that endocannabinoids help prevent — or control — intestinal inflammation. These findings suggest that such compounds might serve the same function in humans.

Wooden Figure belly ache.

Image credits Wolfgang Claussen.

Cannabis users have long reported that the drug helps reduce the symptoms of inflammatory bowel disease (IBD). New research published by a team from the University of Massachusetts Medical School and the University of Bath explored why. Their findings reveal a novel mechanism that governs inflammation of the gut and may result in a new class of drugs to treat diseases that involve intestinal inflammation.

Pot gut

“There’s been a lot of anecdotal evidence about the benefits of medical marijuana, but there hasn’t been a lot of science to back it up,” said Beth A. McCormick, PhD and paper co-author.

“For the first time, we have an understanding of the molecules involved in the process and how endocannabinoids and cannabinoids control inflammation. This gives clinical researchers a new drug target to explore to treat patients that suffer from inflammatory bowel diseases, and perhaps other diseases, as well.”

While reports of marijuana helping alleviate gut inflammation are quite numerous, evidence to explain why aren’t. This study is the first to identify a biological mechanism that underpins this effect, helping to explain why cannabis reduces intestine inflammation for conditions such as ulcerative colitis and Crohn’s disease.

According to the team, gut inflammation is regulated by two distinct processes that each act in turn depending on the conditions in the intestinal environment.

The first process (which was identified in previous research) kick-starts an aggressive immune response in the intestine. This helps our bodies eliminate pathogens, but overzealous immune cells can also damage the lining of the gut by attacking cells indiscriminately.

The second process turns off this inflammation response. The response is spread by special molecules that move across the epithelial cells in the intestine (i.e. the lining) via the same channels that help flush out toxins from the gut.

The key here is that this second process involves a molecule called an endocannabinoid — which is very similar to the cannabinoids found in cannabis. If there aren’t enough endocannabinoids, inflammation won’t shut down and the body’s immune cells run amok on our guts’ lining.

McCormick and colleagues believe that because cannabis use introduces cannabinoids into the body, these molecules might help relieve gut inflammation as the naturally produced endocannabinoids normally would.

“We need to be clear that while this is a plausible explanation for why marijuana users have reported cannabis relieves symptoms of IBD, we have thus far only evaluated this in mice and have not proven this experimentally in humans,” she adds.

However, the team hopes that these findings will result in new drugs to help treat bowel diseases in humans.

The paper “Intestinal P-glycoprotein exports endocannabinoids to prevent inflammation and maintain homeostasis” has been published in the Journal of Clinical Investigation.

New studies describe a link between influenza and parotitis

Parotitis is the inflammation and swelling of the salivary glands. 

Parotitis is the inflammation and swelling of one or both salivary glands. The only known cause of epidemic parotitis among humans is mumps, a vaccine-preventable disease caused by the mumps virus, a member of the Rubulavirus genus of the Paramyxoviridae family. Before the approval of the mumps vaccine in the late 1960s, mumps was one of the most frequently reported diseases during childhood. Since 1990, the Advisory Committee on Immunization Practices (ACIP) has recommended children routinely receive two doses of measles–mumps–rubella vaccine (MMR) and this had a significant impact on reducing the occurrence of mumps.

According to two new articles published in Clinical Infectious Diseases, parotitis may be a complication of infection with the influenza virus. Both studies reviewed recent non-mumps related cases of parotitis following influenza and other viral infections, showing that after mumps had been ruled out, doctors and healthcare professionals should consider influenza when examining a patient who presents with parotitis. Furthermore, the investigators found that influenza A(H3N2), the flu strain behind the northern hemisphere 2017-2018 severe flu season, may be more likely to cause parotitis.

The first study by researchers from the US Centers for Disease Control and Prevention (CDC) investigated the etiology and clinical features of parotitis not caused by mumps during the 2014-2015 US influenza season in 320 American cases. The cases occurred in 27 states, mostly in men (65%). Almost two-thirds of patients (64%) were under 20 years of age. The subjects answered a questionnaire about their illness, and the CDC tested patient samples for several viruses. Viruses were detected in 210 buccal swab specimens (71%) of 294 non-mumps parotitis (NMP) patients with adequate samples for testing. These included 156 influenza A(H3N2), 42 human herpesvirus 6B (HHV6B), 32 Epstein-Barr virus (EBV), 8 human parainfluenza virus type 2 (HPIV2), 2 human parainfluenza virus type 3 (HPIV3), 3 adenovirus, 4 herpes simplex virus type 1 (HSV-1), and 1 herpes simplex virus type 2 (HSV-2). Influenza A(H3N2), HHV6B and EBV were the most frequently co-detected viruses. Because buccal swab specimens are not optimal for detecting influenza RNA, it is possible that the results underestimate the presence of influenza.

The second study by the same group of CDC researchers focused on interviews with 50 patients who had parotitis and were lab-confirmed to have an influenza infection between February to April of 2015. The results were compared with responses from 124 patients with lab-confirmed influenza infections that did not have parotitis. Patients described painful facial swelling, consistent with acute parotitis, which developed shortly after the onset of systemic or respiratory symptoms. Facial swelling lasted for about four days before subsiding. Seven cases were severe enough for the patients to be hospitalized during their illness, this includes two patients who were admitted to the intensive care unit (ICU). Their findings suggest that it may be prudent to include influenza in the differential diagnoses among patients who present with acute parotitis, particularly during flu seasons where influenza A(H3N2) is the dominant strain circulating.

So does the influenza virus cause parotitis?

Other reports of influenza A (H3N2) infection among patients with parotitis during the same flu season in Canada, England, and Scotland show that there is consistency.

In the accompanying commentary by Andrew Pavia, MD, of the Division of Pediatric Infectious Diseases at the University of Utah in Salt Lake City, he noted that the presence of the influenza virus detected in over half of patients with non-mumps parotitis adds strength to the association between flu and parotitis but does not prove it. He wrote, “In the absence of experimental data or the demonstration that influenza virus replicates in salivary glands, it will be hard to prove to a high degree of scientific certainty that influenza causes parotitis.” However, these two studies “strongly suggest that parotitis can be added to the long list of syndromes caused by influenza.”

Knee arthritis has doubled since 1950, and we don’t really know why

Aging and obesity alone cannot explain it.


Arthritis is an inflammation of the joints (or another area where the bones come together). It’s often a chronic condition which typically starts off in the hands or feet, and most often ends up affecting the knees. It’s estimated that one in five Americans over 45 suffer from knee arthritis, and similar figures are reported in many parts of the world.

Initially, this was thought to be a consequence of aging — people lived to older ages, and therefore started suffering more from “old age diseases.” Obesity is also thought to play a role — the more you weigh, the more pressure you put on your joints. But a new study found that these factors alone cannot explain the rise in knee arthritis prevalence.

Stretching my knees

Image credits: BruceBlaus.

Ian Wallace is a paleoanthropologist at Harvard University who studies how human health and diseases have changed over time. He was aware that knee arthritis is often associated with obesity and aging, but wanted to see how these and other factors affected the prevalence of obesity through the years. So he and his colleagues studied several thousand American skeletons, from pre-industrial, early industrial, and post-industrial periods. They were specifically looking at the wear and tear in the skeleton’s knees. The age and body mass index were also assessed and through statistical processing, the impact of obesity and age was removed.

Wallace and colleagues found that 18 percent of the skeletons from the post-industrial ages (1950) had signs of advanced arthritis, compared to six and eight percent of the early industrial and prehistoric bones, respectively. The statistical model showed that neither aging nor obesity can explain the phenomenon.

“It points to this mysterious conclusion: A lot of cases of osteoarthritis, which we thought might be inevitable, may be preventable… and are due to unknown factors,” Wallace says.

Of course, both obesity and aging take their toll — no one’s saying they just don’t matter. But what this study shows is that there’s something else we’re missing.

What could it be?

The study didn’t attempt to explain the findings, but it’s not very difficult to speculate. Wallace too says that lack of physical activity is a very likely culprit. Since the 1950s, office jobs have multiplied dramatically, more and more cars flood the streets, and physical activity has declined accordingly. Sitting down is also a possible culprit. David Felson, study co-author, a renowned arthritis expert and physician at Boston University comments:

“Our joints don’t do well when they aren’t active much of the time,” Felson says.

But that might not tell the whole story. Inflammation might also be at blame. Arthritis itself is an inflammation, but different inflammations, while a natural reaction, promote injury and prevent proper healing. Francis Berenbaum, a researcher and physician at Pierre and Marie Curie University and  AP-HP hospital in Paris, France, who wasn’t involved in the study, believes an unhealthy diet might also be at blame. The same diet (high in processed foods and sugars) that’s favoring diabetes and heart diseases might also be contributing to arthritis. Other factors, such as walking more on hard surfaces such as concrete or asphalt or concrete might also contribute, but at the moment, the truth is we don’t really know.

“I study this, and I don’t know… what [more] can be done to prevent it,” Felson adds.

For now, your best bet is to keep a healthy diet and be physically active.

Journal Reference: Ian J. Wallace, Steven Worthington, David T. Felson, Robert D. Jurmain, Kimberly T. Wren, Heli Maijanen, Robert J. Woods, and Daniel E. Lieberman — Knee osteoarthritis has doubled in prevalence since the mid-20th century. doi: 10.1073/pnas.1703856114

Europeans picked up a customized immune system by having sex with Neanderthals

Researchers have discovered that people of European and African descent have very different immune responses to infections. They believe these traits could be the result of modern humans breeding with Neanderthals after leaving Africa.

Image credits Paul Hudson / Flickr.

Sometime between one hundred to a few tens of thousands of years ago, as modern humans migrated out of Africa, they met strange peoples which weren’t completely like them, but not too different either — the Neanderthals. So, naturally, they had sex with them.

The genes we acquired in that exchange may be responsible for a whole range of diseases, but it’s possible they gave our ancestors the means to better adapt to their new environment. Scientists studying the immune system of humans today have found that people of European descent have significantly different immune responses from their African counterparts — a direct consequence of the exchange, they believe.

The finding could explain why Africans generally have more robust immune systems than Europeans, but also why they’re more predisposed to certain autoimmune conditions.

“I was expecting to see ancestry-associated differences in immune response but not such a clear trend towards an overall stronger response to infection among individuals of African descent,” says University of Montreal geneticist and paper co-author Luis Barreiro.

Barreiro’s team examined samples taken from 175 American patients, roughly half and half of African and European ancestry. They extracted macrophages from their blood — white cells that kill pathogens by “eating” them — and infected the cells with Listeria and Salmonella. They let them go about their business for 24 hours, then analyzed them.

The cells retrieved from the African group had reduced the bacterial growth three times faster than the European group thanks to a stronger inflammatory response. That’s a definite plus when combating infections, but the team points out it’s a double edged sword.

“The immune system of African Americans responds differently, but we cannot conclude that it is better,” Barreiro said, “since a stronger immune response also has negative effects, including greater susceptibility to autoimmune inflammatory diseases such as Crohn’s disease.”

The team also examined the genetic makeup of the cells’ active genes, and found a link between the European sample and Neanderthal DNA — but didn’t find any similar link in the African sample.

The team says that when early humans migrated into Europe around 100,000 years ago, they encountered a continent already colonized by the Neanderthal. Finding traces of their DNA in modern European subjects suggests that the two species actively bred with each other. It makes sense, too. The new genes would have offered our ancestors an evolutionary edge in Europe, where environmental conditions were very different from those in Africa. A lower inflammatory response would also make more sense in the colder climate compared to Africa’s sweltering heat, which promotes infections.

“Our results suggest that the immune systems of African- and European-descended individuals have evolved to better respond to the specific needs imposed by their specific environments,” Barreiro told Live Science.

“What is advantageous in one context is likely to be detrimental in another.”

Too much of a good thing

A separate study also found a lower inflammatory tendency in monocytes against bacterial and viral threats in people of European descent compared to those from Africa. The study included 200 participants from France. The team, led by Lluis Quintana-Murci from the Institut Pasteur, also tied the differences to Neanderthal-like genes in the European participants. In broad lines, the results are the same. The French team also suggests that a powerful inflammatory response could actually be dangerous in Europe, so this effect could have provided an inherent evolutionary benefit — weeding out the more inflammatory-prone genes over time.

“Reducing immune inflammatory responses is a way to avoid autoimmunity, inflammatory, and allergic reactions,” Quintana-Murci told ResearchGate.

“Finding that reduced immune responses has conferred an advantage highlights the tradeoff between recognising pathogens while avoiding exacerbated, aberrant reactions that can be also harmful for the host.”

Both studies say more work needs to be done before we understand where these differences stem from. But it could help us develop things like personalized treatments or medications tailored for certain ethnicities’ needs.

“There is still much to do,” says Barreiro. “[Genetics] explains only about 30 percent of the observed differences in immune responses. Our future studies should focus on other factors, emphasising the influence of the environment and our behaviour.”

Barreiro’s and Quintana-Murci’s studies are published in the journal Cell.