Nav: Home

New way to fight sepsis: Rev up patients' immune systems

March 08, 2018

While many people have never heard of sepsis, it causes about 250,000 deaths annually in the United States. The condition develops when an infection triggers an overwhelming immune response, ultimately wreaking havoc on the immune system. Standard treatment involves high doses of antibiotics that fight the infection, but they often don't work well and fail to boost the body's immune defenses.

Now, a small clinical trial led by researchers at Washington University School of Medicine in St. Louis shows that a drug that revs up the immune system holds promise. The approach goes against the grain of earlier strategies that have relied on antibiotics and inflammatory medications to tamp down the immune system.

Their findings are published March 8 in the journal JCI Insight.

"Mortality rates from sepsis have remained essentially the same over the last 50 years," said senior investigator Richard S. Hotchkiss, MD, a professor of anesthesiology, of medicine and of surgery. "Hundreds of drugs have been tried and have failed. It may sound counterintuitive when inflammation is such a problem early in sepsis, but our approach is to stimulate certain immune cells to help the patient's system take control of the infection."

The trial involved 27 sepsis patients, ages 33 to 82, who were treated at Barnes-Jewish Hospital in St. Louis, Vanderbilt University Medical Center in Nashville or two medical centers in France -- Dupuytren University Hospital in Limoges and Edouard Herriot Hospital in Lyon. Although the study was too small to see a statistical benefit in mortality, the researchers noted an improved immune response in patients who were given a drug to beef up their immunity.

The patients were treated with a drug made of interleukin-7 (IL-7), which enhances the proliferation and survival of two types of immune cells: CD4 and CD8. These cells are important because they recruit other immune cells to fight severe infections that can lead to organ failure and death.

"Patients who develop the most serious form of sepsis, called septic shock, often have very low counts of these key immune cells," said co-investigator Edward R. Sherwood, MD, PhD, a professor of anesthesiology at Vanderbilt. "We believe that could play a role in the development and course of sepsis because without those cells, patients aren't able to clear as much harmful bacteria."

The patients in the trial, who were hospitalized and severely ill with septic shock, were randomly assigned to one of two therapies. Seventeen patients received the IL-7 drug, and 10 received a standard treatment. Those who received the drug experienced a threefold to fourfold increase in CD4 and CD8 counts.

"Even though the study was small, we were encouraged that IL-7 helped restore key cells in the immune systems of these patients," said Andrew H. Walton, a staff scientist in the Hotchkiss lab and co-author of the study. "Overall, that should help improve patient survival."

The researchers showed that IL-7 boosts adaptive immunity, in which CD4 and CD8 T cells help recruit other immune cells -- called macrophages, monocytes, neutrophils and dendritic cells -- to kill bacteria that cause infections. Traditional approaches to sepsis therapy do not address the critical problem of patients' severely compromised immune systems. Without restoring immune function, Hotchkiss said, many patients develop lingering infections and are helpless to fight any new infections.

"We know that 40 percent of patients die in the 30- to 90-day period after the initial septic infection," Hotchkiss said. "Their bodies can't fight secondary infections, such as the blood infections and staph infections that can develop later on because their immune systems are shot. By strengthening adaptive immunity with IL-7 and increasing the numbers of CD4 and CD8 cells available to help fight infections, we think this approach can make a big difference."

Hotchkiss credits recent approaches to cancer treatment as evidence that this strategy for sepsis therapy may be a game changer for many patients. Several cancer researchers have begun using IL-7 to rev up a patient's own immune system to fight cancer. In addition, under compassionate-use guidelines, IL-7 has been given to some critically ill patients with serious viral infections and has successfully restored their CD4 and CD8 counts while improving survival.

As a next step, Hotchkiss and Sherwood are planning a larger trial to determine whether the same holds true for sepsis patients. They estimate a study involving 300 to 400 patients should have the statistical strength to determine whether IL-7 can improve survival rates.
-end-
Francois B, et al. Interleukin-7 restores lymphocytes in septic shock-the IRIS-7 randomized clinical trial. JCI Insight, vol. 3 (5), March 8, 2018. https://doi.org/10.1172/jci.insight.98960

This work was supported by the National Institute of General Medical Sciences of the National Institutes of Health (NIH), grant numbers GM44118 and GM55194. Additional support from Revimmune, manufacturer of the recombinant human IL7 drug (CYT107).

Washington University School of Medicine's 2,100 employed and volunteer faculty physicians also are the medical staff of Barnes-Jewish and St. Louis Children's hospitals. The School of Medicine is one of the leading medical research, teaching and patient-care institutions in the nation, currently ranked seventh in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children's hospitals, the School of Medicine is linked to BJC HealthCare.

Washington University School of Medicine

Related Immune System Articles:

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.
Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.
COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.
Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.
Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.
Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.
Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.
How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.
Immune system upgrade
Theoretically, our immune system could detect and kill cancer cells.
Using the immune system as a defence against cancer
Research published today in the British Journal of Cancer has found that a naturally occurring molecule and a component of the immune system that can successfully target and kill cancer cells, can also encourage immunity against cancer resurgence.
More Immune System News and Immune System Current Events

Trending Science News

Current Coronavirus (COVID-19) News

Top Science Podcasts

We have hand picked the top science podcasts of 2020.
Now Playing: TED Radio Hour

Warped Reality
False information on the internet makes it harder and harder to know what's true, and the consequences have been devastating. This hour, TED speakers explore ideas around technology and deception. Guests include law professor Danielle Citron, journalist Andrew Marantz, and computer scientist Joy Buolamwini.
Now Playing: Science for the People

#576 Science Communication in Creative Places
When you think of science communication, you might think of TED talks or museum talks or video talks, or... people giving lectures. It's a lot of people talking. But there's more to sci comm than that. This week host Bethany Brookshire talks to three people who have looked at science communication in places you might not expect it. We'll speak with Mauna Dasari, a graduate student at Notre Dame, about making mammals into a March Madness match. We'll talk with Sarah Garner, director of the Pathologists Assistant Program at Tulane University School of Medicine, who takes pathology instruction out of...
Now Playing: Radiolab

What If?
There's plenty of speculation about what Donald Trump might do in the wake of the election. Would he dispute the results if he loses? Would he simply refuse to leave office, or even try to use the military to maintain control? Last summer, Rosa Brooks got together a team of experts and political operatives from both sides of the aisle to ask a slightly different question. Rather than arguing about whether he'd do those things, they dug into what exactly would happen if he did. Part war game part choose your own adventure, Rosa's Transition Integrity Project doesn't give us any predictions, and it isn't a referendum on Trump. Instead, it's a deeply illuminating stress test on our laws, our institutions, and on the commitment to democracy written into the constitution. This episode was reported by Bethel Habte, with help from Tracie Hunte, and produced by Bethel Habte. Jeremy Bloom provided original music. Support Radiolab by becoming a member today at Radiolab.org/donate.     You can read The Transition Integrity Project's report here.