ed normal, adult levels of two key cytokines ?TNF-alpha and IL-12 ?and another immune-system stimulant, CD40.
"These findings suggest that agents that stimulate TLR8 could be used to enhance immune responses in newborns, perhaps as adjuvants given along with vaccines," Levy says. "We plan to test this approach in animals, and eventually in human babies."
Levy notes that the ability to vaccinate newborns ?rather than wait until they reach 2 months of age ?would provide important global health benefits. "Birth is a point of contact with healthcare systems," he says. "Families may not see a health care provider after that. From a global health perspective, if you can give a vaccine at birth, a much higher percentage of the population can be covered."
Conceivably, TLR8 stimulators could also be given alone in special circumstances ?to help a baby fight off an infection in progress, or as a preventive measure in the event of a disease outbreak or bio-terrorist threat, Levy adds.
Levy's team is uncovering other differences between the newborn and adult immune systems that could lead to additional targets for drugs or vaccines. A related paper, to be published soon in the journal Pediatric Research, finds that when newborns' TLRs are stimulated during the first week of life, their white cells' production of the cytokine IL-6, which inhibits parts of the immune response, is greater than that in adults.
A third study, to be published in the Journal of Immunology, finds that newborns' cord blood also has high levels of adenosine, providing an explanation for newborns' altered immune response: adenosine alters the physiology of white cells to suppress production of TNF-alpha (but not of IL-6) when TLRs are stimulated. When Levy's team used antagonists to inhibit adenosine's activity, newborns' white blood cells produced normal, adult levels of TNF-alpha in response to bacterial and viral triggers. "In the future, we could try to bl
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Source:Children's Hospital Boston
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