Sepsis, an exaggerated and overwhelming inflammatory response to infection, is a major worldwide killer of babies in the first four weeks of life (neonatal period).
Now, researchers at Vanderbilt University Medical Center (VUMC) and the University of Florida in Gainesville have discovered a potential way to intervene in the “cytokine storm” that contributes to this deadly tsunami in vulnerable neonates.
Their report, published last month in the Proceedings of the National Academy of Sciences (PNAS), cracked “the code” of neonatal sepsis based on interleukin-18 and interleukin-17 (IL-18 and IL-17), two members of the immunologically active family of interleukin proteins that, in response to infection, can trigger a potentially deadly inflammatory response in multiple organs.
They found that mice lacking the gene for IL-18 were “highly protected” from sepsis, that giving IL-18 in the context of sepsis led to a rise in IL-17 levels, and that blocking the IL-17 receptor prevented the “enhancement” of sepsis mortality by IL-18.
“Short-term blockade (of IL-17) could prove life-saving in the vulnerable neonate population,” the researchers concluded. “Pharmaceutical targeting of the IL-17 network may emerge as the preferred candidate for improving neonatal sepsis survival.”
James Wynn, M.D., associate professor of Pediatrics and Experimental Medicine at the University of Florida, was the paper’s first author. Daniel Moore, M.D., Ph.D., assistant professor of Pediatrics and of Pathology, Microbiology and Immunology at VUMC, was the senior author.
Other VUMC faculty members who contributed to the study were John Benjamin, MBBS, MPH, Jacek Hawiger, M.D., Ph.D., Erin Plosa, M.D., Edward Sherwood, M.D., Ph.D., and Jörn-Hendrik Weitkamp, M.D.
