Immune system simulation shows need for multi-target treatments for sepsis

February 15, 2018, Public Library of Science

Using a computational model of the human immune system, scientists have shown that efforts to combat sepsis might be more effective if they targeted multiple steps in the molecular processes that drive the illness. This finding is presented in PLOS Computational Biology.

Sepsis is a dysregulation of the body's normal inflammatory response to injury and infection. People with may receive oxygen and , as well as antibiotics to fight the underlying infection, but the condition kills 28 to 50 percent of affected patients. So far, drugs developed to attack the that underpin sepsis have not shown clinical success.

To explore the molecular challenges of sepsis treatment, Chase Cockrell and Gary An of the University of Chicago employed a of the human immune system, which they had previously developed specifically to investigate systemic inflammation. The model simulates how and signaling molecules behave during sepsis, as well as the effects of disrupting various parts of these processes.

Using their model, the researchers showed that disrupting a single signaling process at a single point (or just a few points) in time would not be adequate to treat sepsis. This may explain why previous attempts that employed such a strategy have not been effective. Instead, the simulation showed, successful treatment would require drugs that frequently target multiple immune system processes.

The model also showed that a "one-size-fits-all" multi-target approach would still be inadequate, and true "precision medicine" would require a treatment to adapt itself based on each patient's individual response. The researchers concluded that computational modeling is necessary to generate the amount of data required by machine-learning algorithms to aid development of effective sepsis drugs.

"This project provides a reality check on how people are currently thinking about trying to treat sepsis at a drug-design level," Cockrell says. "It will hopefully help focus research into those areas that will actually provide a path towards effective therapy, such as high-resolution diagnostics and sampling, and realizing that there is no 'one-size-fits-all' answer."

Explore further: Scientists find potential mechanism for deadly, sepsis-induced secondary infection

More information: Cockrell RC, An G (2018) Examining the controllability of sepsis using genetic algorithms on an agent-based model of systemic inflammation. PLoS Comput Biol 14(2): e1005876.

Related Stories

Scientists find potential mechanism for deadly, sepsis-induced secondary infection

September 14, 2017
In mice, an infection-induced condition known as sepsis may increase the risk of life-threatening secondary infection by preventing recruitment of infection-fighting cells to the skin, according to new research published ...

Cancer drug found to offer promising results in treating sepsis in test mice

October 19, 2017
(Medical Xpress)—A combined team of researchers from China and the U.S. has found that a drug commonly used to treat lung cancer in humans offers a degree of protection against sepsis in test mice. In their paper published ...

Researchers map links between salmonella and sepsis

September 16, 2016
Research by industrial engineering and biology researchers at Kansas State University marks a significant milestone in the battle against sepsis, the second highest cause of death in intensive care units in the U.S.

Scientists illuminate role of staph toxins in bacterial sepsis

February 2, 2017
Staphylococcus epidermidis bacteria are a significant health concern for hospitalized infants, children and anyone with implanted medical devices. The bacteria—typically skin dwellers—can infect the bloodstream and cause ...

Erectile dysfunction drugs could protect liver from sepsis-induced damage

January 29, 2015
Drugs that are on the market to treat erectile dysfunction (ED) could have another use—they might be able to protect the liver from damage caused by sepsis, a systemic inflammatory response to infection, say researchers ...

Alterations in fatty acid synthesis linked to sepsis inflammation

January 9, 2015
Sepsis is a leading cause of death for patients in intensive care units. The excessive systemic inflammation in individuals with sepsis damages organs and can lead to death. Therapeutic options for sepsis are limited and ...

Recommended for you

Quintupling inhaler medication may not prevent asthma attacks in children

March 19, 2018
Children with mild to moderate asthma do not benefit from a common practice of increasing their inhaled steroids at the first signs of an asthma exacerbation, according to clinical trial results published in The New England ...

How allergens trigger asthma attacks

March 19, 2018
A team of Inserm and CNRS researchers from the Institute of Pharmacology and Structural Biology have identified a protein that acts like a sensor detecting allergens in the respiratory tract that are responsible for asthma ...

Single steroid-bronchodilator treatment for control and rescue improves persistent asthma

March 19, 2018
When it comes to treating teens and adults with persistent asthma, using a single corticosteroid and long-acting bronchodilator treatment for both daily asthma control and for rescue relief during sudden asthma attacks is ...

Obesity and health problems: New research on a safeguard mechanism

March 16, 2018
Obesity and its negative impacts on health - including metabolic syndrome, type-2 diabetes mellitus and cardiovascular complications - are a global pandemic (Taubes, 2009). The worldwide incidence of obesity has more than ...

Immune system 'double agent' could be new ally in cancer fight

March 16, 2018
St. Jude Children's Research Hospital scientists have discovered that an enzyme called TAK1 functions like a "double agent" in the innate immune response, serving as an unexpected regulator of inflammation and cell death. ...

Artificial sweetener Splenda could intensify symptoms in those with Crohn's disease

March 15, 2018
In a study that has implications for humans with inflammatory diseases, researchers from Case Western Reserve University School of Medicine and colleagues have found that, given over a six-week period, the artificial sweetener ...


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.