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Credit: Graham Colm
An immune marker may help predict which child trauma patients are likely to develop a hospital-acquired infection, and it may also provide new insight into immune response following transfusion.
In a small study, blood samples from critically ill children showed decreased production of TNF-alpha, a cytokine that’s part of the first line of defense in the innate immune system, when compared to samples from healthy control children.
In addition, TNF-alpha production was lower among children who received transfusions with older blood, compared to children who received fresher blood.
Mark W. Hall, MD, of Nationwide Children’s Hospital in Columbus, Ohio, and his colleagues reported these findings in Shock.
The researchers had collected blood samples from 21 healthy children and 76 critically injured children aged 18 years or younger. The team then exposed each sample to lipopolysaccharide (LPS), a known stimulant of the immune response. When healthy cells are exposed to LPS, it prompts the production of TNF-alpha.
When they analyzed the immune response, the researchers found that blood samples from the healthy children responded normally to LPS, producing high levels of TNF-alpha.
Samples from the patients with critical injuries all showed at least a moderate decrease in the production of TNF-alpha. But the children who went on to develop an infection showed a much more severe and persistent drop in TNF-alpha following injury.
While the findings strongly suggest that infection risk is associated with immune system function after critical injury, they don’t explain what’s causing the malfunction. Dr Hall’s team is investigating that question now.
Transfusion implications
The research also highlighted another issue that may affect the immune response in critical illness. The team found that patients who received a transfusion of blood stored for more than 2 weeks had a lower level of TNF-alpha production than kids whose transfused blood was less than 2 weeks old, regardless of the severity of their original injury.
This supports a study published by Dr Hall and his colleagues in 2012 in Transfusion. The study showed the same immunosuppressive effect in a human cell culture model.
Dr Hall plans to look into this further through his work with a multi-institutional effort called The Pediatric Critical Care Blood Research Network (BloodNet). The group is studying, among other things, what impact blood transfusions have on immune function.
“There’s a whole line of research in which we’re involved that is dedicated to understanding the effects of transfusion in critical illness,” he said. “It’s not clear yet if blood transfusions are immunosuppressive, but our work so far suggests that blood becomes more immunosuppressive the longer it sits on the shelf.”
Reversing immunosuppression
Yet another element to the study involves reversing the immunosuppression that follows critical injury or illness. The researchers took 3 blood samples in which TNF-alpha production was decreased and cultured them with GM-CSF.
Once treated, the cells began to produce normal levels of TNF-alpha—an indication that the immunosuppression had been reversed.
Dr Hall is now leading a phase 4 clinical trial of GM-CSF to reverse immunosuppression in critically injured patients aged 1 to 21 years old.
Although findings from that project won’t be ready for another year or so, the results in the Shock article seem to offer yet another weapon in physicians’ arsenal when caring for critically ill and injured children, Dr Hall said.
“We have certainly made headway in reducing preventable infections through programs such as our own Zero Hero initiative,” he noted.
“But what this paper suggests is that it’s also important to consider the patient’s immune system and how well they are able to fight off infection. We believe that critical illness- and injury-related immune suppression may be reversible with beneficial effects on clinical outcomes.” 
Credit: Graham Colm
An immune marker may help predict which child trauma patients are likely to develop a hospital-acquired infection, and it may also provide new insight into immune response following transfusion.
In a small study, blood samples from critically ill children showed decreased production of TNF-alpha, a cytokine that’s part of the first line of defense in the innate immune system, when compared to samples from healthy control children.
In addition, TNF-alpha production was lower among children who received transfusions with older blood, compared to children who received fresher blood.
Mark W. Hall, MD, of Nationwide Children’s Hospital in Columbus, Ohio, and his colleagues reported these findings in Shock.
The researchers had collected blood samples from 21 healthy children and 76 critically injured children aged 18 years or younger. The team then exposed each sample to lipopolysaccharide (LPS), a known stimulant of the immune response. When healthy cells are exposed to LPS, it prompts the production of TNF-alpha.
When they analyzed the immune response, the researchers found that blood samples from the healthy children responded normally to LPS, producing high levels of TNF-alpha.
Samples from the patients with critical injuries all showed at least a moderate decrease in the production of TNF-alpha. But the children who went on to develop an infection showed a much more severe and persistent drop in TNF-alpha following injury.
While the findings strongly suggest that infection risk is associated with immune system function after critical injury, they don’t explain what’s causing the malfunction. Dr Hall’s team is investigating that question now.
Transfusion implications
The research also highlighted another issue that may affect the immune response in critical illness. The team found that patients who received a transfusion of blood stored for more than 2 weeks had a lower level of TNF-alpha production than kids whose transfused blood was less than 2 weeks old, regardless of the severity of their original injury.
This supports a study published by Dr Hall and his colleagues in 2012 in Transfusion. The study showed the same immunosuppressive effect in a human cell culture model.
Dr Hall plans to look into this further through his work with a multi-institutional effort called The Pediatric Critical Care Blood Research Network (BloodNet). The group is studying, among other things, what impact blood transfusions have on immune function.
“There’s a whole line of research in which we’re involved that is dedicated to understanding the effects of transfusion in critical illness,” he said. “It’s not clear yet if blood transfusions are immunosuppressive, but our work so far suggests that blood becomes more immunosuppressive the longer it sits on the shelf.”
Reversing immunosuppression
Yet another element to the study involves reversing the immunosuppression that follows critical injury or illness. The researchers took 3 blood samples in which TNF-alpha production was decreased and cultured them with GM-CSF.
Once treated, the cells began to produce normal levels of TNF-alpha—an indication that the immunosuppression had been reversed.
Dr Hall is now leading a phase 4 clinical trial of GM-CSF to reverse immunosuppression in critically injured patients aged 1 to 21 years old.
Although findings from that project won’t be ready for another year or so, the results in the Shock article seem to offer yet another weapon in physicians’ arsenal when caring for critically ill and injured children, Dr Hall said.
“We have certainly made headway in reducing preventable infections through programs such as our own Zero Hero initiative,” he noted.
“But what this paper suggests is that it’s also important to consider the patient’s immune system and how well they are able to fight off infection. We believe that critical illness- and injury-related immune suppression may be reversible with beneficial effects on clinical outcomes.”
Credit: Graham Colm
An immune marker may help predict which child trauma patients are likely to develop a hospital-acquired infection, and it may also provide new insight into immune response following transfusion.
In a small study, blood samples from critically ill children showed decreased production of TNF-alpha, a cytokine that’s part of the first line of defense in the innate immune system, when compared to samples from healthy control children.
In addition, TNF-alpha production was lower among children who received transfusions with older blood, compared to children who received fresher blood.
Mark W. Hall, MD, of Nationwide Children’s Hospital in Columbus, Ohio, and his colleagues reported these findings in Shock.
The researchers had collected blood samples from 21 healthy children and 76 critically injured children aged 18 years or younger. The team then exposed each sample to lipopolysaccharide (LPS), a known stimulant of the immune response. When healthy cells are exposed to LPS, it prompts the production of TNF-alpha.
When they analyzed the immune response, the researchers found that blood samples from the healthy children responded normally to LPS, producing high levels of TNF-alpha.
Samples from the patients with critical injuries all showed at least a moderate decrease in the production of TNF-alpha. But the children who went on to develop an infection showed a much more severe and persistent drop in TNF-alpha following injury.
While the findings strongly suggest that infection risk is associated with immune system function after critical injury, they don’t explain what’s causing the malfunction. Dr Hall’s team is investigating that question now.
Transfusion implications
The research also highlighted another issue that may affect the immune response in critical illness. The team found that patients who received a transfusion of blood stored for more than 2 weeks had a lower level of TNF-alpha production than kids whose transfused blood was less than 2 weeks old, regardless of the severity of their original injury.
This supports a study published by Dr Hall and his colleagues in 2012 in Transfusion. The study showed the same immunosuppressive effect in a human cell culture model.
Dr Hall plans to look into this further through his work with a multi-institutional effort called The Pediatric Critical Care Blood Research Network (BloodNet). The group is studying, among other things, what impact blood transfusions have on immune function.
“There’s a whole line of research in which we’re involved that is dedicated to understanding the effects of transfusion in critical illness,” he said. “It’s not clear yet if blood transfusions are immunosuppressive, but our work so far suggests that blood becomes more immunosuppressive the longer it sits on the shelf.”
Reversing immunosuppression
Yet another element to the study involves reversing the immunosuppression that follows critical injury or illness. The researchers took 3 blood samples in which TNF-alpha production was decreased and cultured them with GM-CSF.
Once treated, the cells began to produce normal levels of TNF-alpha—an indication that the immunosuppression had been reversed.
Dr Hall is now leading a phase 4 clinical trial of GM-CSF to reverse immunosuppression in critically injured patients aged 1 to 21 years old.
Although findings from that project won’t be ready for another year or so, the results in the Shock article seem to offer yet another weapon in physicians’ arsenal when caring for critically ill and injured children, Dr Hall said.
“We have certainly made headway in reducing preventable infections through programs such as our own Zero Hero initiative,” he noted.
“But what this paper suggests is that it’s also important to consider the patient’s immune system and how well they are able to fight off infection. We believe that critical illness- and injury-related immune suppression may be reversible with beneficial effects on clinical outcomes.”