In several of our gene expression studies we have reported that pediatric septic shock is characterized by early and persistent repression of gene programs that either directly participate in zinc homeostasis, or depend on zinc homeostasis for normal function. Given the established role of normal zinc homeostasis for normal functioning of the immune system, these observations have raised the possibility of zinc supplementation in sepsis. Several studies have documented a beneficial effect of zinc supplementation in animal models of sepsis. We are currently collaborating in a Phase 1 clinical trial of zinc supplementation in critical illness (NCT01062009). Natalie Cvijanovich, MD, from Children’s Hospital & Research Center Oakland is the principal investigator for this Phase 1 trial, and Alexander Vinks, PharmD, PhD, from the Division of Clinical Pharmacology at Cincinnati Children’s is providing expertise in the area of pharmacokinetics and pharmacodynamics.
- Cvijanovich, N.Z., J.C. King, H.R. Flori, G. Gildengorin, S.A. Vinks, and H.R. Wong. Safety and dose-escalation study of parenteral zinc supplementation in pediatric critical illness. JPEN J Parenter Enteral Nutr. 2015 (in press).
- Nowak, J.E., K. Harmon, C.C. Caldwell, and H.R. Wong. Prophylactic zinc supplementation reduces bacterial load and improves survival in a murine model of sepsis. Pediatr Crit Care Med. 13:e323-329, 2012.
- Cvijanovich, N, T.P. Shanley, R. Lin, G.L. Allen, N.J. Thomas, P. Checchia, N. Anas, R.J. Nowak, J.E., K. Harmon, C.C. Caldwell, and H.R. Wong. Prophylactic zinc supplementation reduces bacterial load and improves survival in a murine model of sepsis. Pediatr Crit Care Med. 13:e323-329, 2012.
- Nowak, J.S. and Wong, H.R. Novel therapeutic agents in pediatric sepsis—zinc. The Open Inflammation Journal. 4:110-114, 2011.
Wong, H.R., Shanley, T.P., Cvijanovich, N., Allen, G.L., Lin, R., Anas, N., Meyer, K., Freishtat, R.J., Monaco, M., Odoms, K. and Sakthivel, B. Genome-wide expression profiling across the pediatric SIRS, sepsis, and septic shock spectrum. Crit Care Med. 37:1558-1566, 2009.
- Cvijanovich, N.Z., King, J.C., Flori, H.R., Gildengorin, G. and Wong, H.R. Zinc homeostasis in pediatric critical illness. Ped Crit Care Med. 10:29-34, 2009.
- Heyland, D.K., Jones, N., Cvijanovich, N., and Wong, H.R. Zinc supplementation in critically ill patients: A key pharmaconutrient?J Parenteral Enteral Nutr. 32:508-519, 2008.
- Freishtat, M. Monaco, K. Odoms, B. Sakthivel, and H.R. Wong, for the Genomics of Pediatric SIRS Investigators. Validating the genomic signature of pediatric septic shock. Physiol Genomics. 34:127-134, 2008.
Shanley, T.P., Cvijanovich, N., Lin, R., Allen, G.L., Thomas, N.J., Doctor, A., Kalyanaraman, M., Tofil, N.M., Penfil, S., Monaco, M., Odoms, K., Barnes, M., Sakthivel, B., Aronow, B.J. and Wong, H.R. Genome-level longitudinal expression of signaling pathways and gene networks in pediatric septic shock. Mol Med. 13:496-508, 2007.
Wong, H.R., Shanley, T.P., Sakthivel, B., Cvijanovich, N., Lin, R., Allen, G.L., Thomas, N.J., Doctor, A., Kalyanaraman, M., Tofil, N.M., Penfil, S., Monaco, M., Tagavilla, M.A., Odoms, K., Dunsmore, K., Barnes, M. and Aronow, B.J., for the Genomics of Pediatric SIRS Investigators. Genome level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome. Physiol Genomics. 30:146-155, 2007.