Cytokines are small proteins produced by the body’s cells that have a big impact on our immune system. Researchers at Boston Children’s Hospital believe that modulating their presence in our bodies could be the key to improving outcomes in life-threatening cases of trauma, hemorrhage and many other conditions including sepsis, which alone impacts nearly one million Americans each year.
The reason? Cells essentially use cytokines to talk to one another. In response to their surroundings, cells release different types of cytokines that encourage inflammatory or anti-inflammatory effects on the body. Infection or trauma causes cells to pump out more cytokines that produce inflammation. Altogether, an escalating chorus of cytokines can sometimes tip a person’s body into overwhelming inflammation that can turn fatal, which is what happens during sepsis.
But what if scientists could remove the problematic cytokines to bring the choir into perfect tune, allowing the immune system to respond with just the right amount of inflammation for healing?
Going with the blood flow
Researchers at Boston Children’s have reported the ability to do just that in a recent issue of JCI Insight. In their paper, they describe a blood filtration system that can selectively remove specific cytokines from circulating blood. In practice, they envision that such a device could someday be used in a personalized manner, able to modulate cytokines in real time based on an individual’s unique cytokine profile.
“The way your body responds to infection or injury — not just the infection or injury itself — plays an important role in determining how or if you are able to recover,” says Brian McAlvin, MD, the first author on the study, who is a clinician-researcher in the Division of Medicine Critical Care at Boston Children’s.
When he isn’t working as a pediatric intensivist, he conducts research with Daniel Kohane, MD, PhD, a principal investigator in the Boston Children’s Department of Anesthesiology, Critical Care and Pain Medicine. Together, their goal has been to combat life-threatening conditions where the body is awash with a cascade of harmful cytokines in response to illness or injury.
“We set out to build a blood-filtering device that could be incorporated into any system that blood flows through,” Kohane says. The team envisions that their blood-filtration device would work in tandem with existing systems utilized by intensive care units. As blood passes through the medical tubing of such devices, the add-on filtration component could be directly exposed to a patient’s blood, providing an opportunity to filter out cytokines.
“For example, systems like ECMO — which bypass the heart and lungs to oxygenate the blood — and dialysis are often used in intensive care units,” Kohane says.
To enable such a blood filtration device, the team took inspiration from antibodies, which are proteins produced by our immune system and able to target almost any unique type of tissue, cell or protein. By decorating the inside of medical tubing with an array of antibodies, the antibodies act like magnets, snatching up problematic cytokines as they flow by.
In animal models and in vitro models using human blood, McAlvin and Kohane brought their blood filtration device to life, calling the technology an “antibody-modified conduit.” In the new paper, they demonstrated that the system was able to selectively remove cytokines from blood and maintain them at reduced levels.
In the future, such an application could have many applications. For a patient with sepsis, that individual’s cytokine profile could inform clinicians which antibody coatings to use with the blood filtration system, enabling removal of the cytokines responsible for that person’s unique inflammatory response.
Aside from personalized clinical applications, Kohane and McAlvin believe that their blood-filtration system could help researchers to better understand the complex interplay of different cytokines and which ones are the most problematic for sepsis and other diseases.
“Moreover, the technology could in principle be applied to remove a wide range of undesirable molecules from the bloodstream,” says McAlvin.
Learn more about research from the Kohane lab.