Tag Archives: cytokine

New trial will try to stop the “cytokine storms” that make COVID-19 cases deadly

Our own immune systems may be to blame for producing some of the worst symptoms of COVID-19, through a process known as a “cytokine storm”. Now, new research plans to fix this.

image credits Engin Akyurt.

The prolonged, high fevers, severe respiratory distress, and lung damage seen in some critically ill patients are actually caused by our immune systems trying (way too hard) to fight off the infection, not by the virus itself. New research at the Johns Hopkins University School of Medicine plans to test the efficiency of a prescription drug called an alpha-blocker as a protection against this process.

A cure for storms

“The approach we’re advocating involves treating people who are at high risk early in the course of the disease, when you know they’re infected but before they have severe symptoms,” says Bert Vogelstein, chief investigator on this project.

The team is setting up a clinical trial with patients ages 45 to 85 who have COVID-19 but who aren’t on a ventilator or in the ICU. These participants will help establish whether alpha blocker prazosin can be used to stop macrophage activation syndrome, or “cytokine storms“, by preventing hyper-inflammation in response to the infection.

Such an effect has been documented in mouse studies, the team explains. If alpha blockers are found efficient in humans as well, they could help keep more people safe at home where they can recover without taking up hospital resources, which are already spread thin.

Exaggerated immune responses aren’t unique to COVID-19, as people with autoimmune diseases and cancer patients receiving immunotherapy can attest.

Cytokines are chemical messengers used by our immune systems to organize against a threat. In moderation, they help immune cells converge to where they’re needed and fight off the infection. However, our bodies also use signaling molecules called catecholamines when a more heavy-handed response is needed, and they trigger the release of more cytokines — this process can form a feedback loop that drives our immune cells berserk.

“It seems that once this process starts, there’s this inability to properly switch it off,” says Maximilian Konig, a rheumatologist at Hopkins who is helping to coordinate the trial.

Alpha blockers interfere with the signaling pathways of cytokines, and Vogelstein’s past research on mice has found that they can be used to lessen cytokine storms and decrease mortality rate without having adverse effects on our immune response.

Giving mice with bacterial infections an alpha-blocker lessened cytokine storms and decreased deaths, Vogelstein’s team reported in the journal Nature in 2018. And, the researchers found, the treatment didn’t seem to harm other aspects of the immune response.

The patients in this trial will be given gradually-increasing doses of prazosin over six days, and will then be monitored to see if they have a lower ICU admission rate or ventilator use than patients who received the standard treatment. The trials will last for 60 days but preliminary data could be available within a few weeks, according to the team.

The paper “Preventing cytokine storm syndrome in COVID-19 using α-1 adrenergic receptor antagonists” has been published in the Journal of Clinical Investigation.

Scientists zoom closer towards understanding chronic fatigue

Are you always feeling extremely tired, for no apparent reason? Scientists might have figured out why — it’s something to do with your cytokines.

Sufferers of chronic fatigue syndrome experience tiredness and unrefreshing sleep. Image via Wikipedia.

Neverending fatigue

Chronic fatigue syndrome (CFS) is a medical condition characterized by unexplainable long-term fatigue, as well as muscle or joint pain, headaches, and other flu-like symptoms. Medics have proposed several mechanisms, but so far, we don’t really know what’s causing it or what the underlying mechanism is. We also don’t really know how common this problem is. Estimates of the number of persons with the condition vary from 7 to 3,000 per 100,000 adults. It’s estimated that in the US, 836,000 to 2.5 million people suffer from the condition. A new study might finally shed some light on this mysterious — and often trivialized — condition.

“Chronic fatigue syndrome can turn a life of productive activity into one of dependency and desolation,” Jose Montoya, M.D., lead author of the new study, published Monday in the Proceedings of the National Academy of Sciences, said in a statement.

He and his collaborators found that people suffering from the syndrome had substantially higher levels of substances called cytokines in their blood. Cytokines are a broad category of small proteins important in cell signaling. They share similarities to hormones, and there’s still an ongoing debate regarding whether the two groups are separate or not. Cytokines also play a role in immune responses to infection and inflammation.

Cytoines been discussed as connected to CFS before, but no theory managed to prevail until now. In past decades, many even believed CFS to be a fictitious condition. Though it has gained some acceptance in recent times, there’s still a shroud of controversy around CFS.

“This is a field that has been full of skepticism and misconception, where patients have been viewed to have invented their disease. These data clearly show the contrary, and demonstrate what can be achieved when we couple good research design with new technology,” Montoya, professor of infectious diseases at Stanford, tells NPR Shots.

Hopefully, this study will help clear the water.

No-rest Cytokines

Montoya and colleagues found levels of 17 cytokines dramatically higher than normal in patients suffering from CFS. Out of these 17, no less than 13 were associated with promoting inflammation. This is highly significant and fits with previous studies that found inflammation and CFS to be connected.

The study has also been well received by other researchers. Dr. Anthony L. Komaroff, a Harvard internist and epidemiologist who has written a commentary to accompany the study, believes this work finally shows that cytokines are what’s causing the symptoms — but there’s a catch.

Previous studies also tried to prove the same thing, but they came out negative. Montoya says that this was happening because the lab tests simply weren’t measuring the right thing. Most commonly, two tests are carried out: the first is sedimentation rate, which is the ability of red blood cells to clump together. This isn’t relevant for CFS. The second is C-reactive protein, which is indicative of cytokine, but only of a single cytokine, and not one that scientists identified in this study. Basically, these are imperfect measures that oversimplify and distort our image of inflammation. We need new tests, new measures, and then we will be able to improve our understanding of complex issues such as chronic fatigue syndrome. While scientific ways to measure the relevant values exist, they need to be translated into an efficient, commercial setting, before they can become widespread.

“There is much to learn,” Komaroff writes, in the journal. “Hopefully, a decade from now, “doctors will know better what to measure and, more importantly, what to do to ease the suffering caused by this illness.”

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