ABSTRACT 232

Abstract

Background and aims: Critically ill children exhibit low levels of plasma zinc (Zn) that correlate with organ and immune dysfunction. Supplementation with intravenous (IV) Zn may provide benefit to patients via anti-inflammatory, immunomodulatory, and endocrine effects. Aims: Using gene expression mosaics, we describe the temporal evolution of gene expression patterns among zinc- and immunity-related genes in a group of critically ill children supplemented with IV zinc. Methods: The study was approved by the IRB. After consent, patients received 750 mg/kg/day IV Zn sulfate in 3 divided doses for 7 days. Blood was collected on Days 1, 3, and 7, and genome wide expression analyses were conducted using whole blood-derived RNA. Results: There was a clear temporal evolution of gene expression patterns across functionally related genes. Specifically, there was increased expression (red intensity) of zinc-related genes and antigen presentation-related genes over the 7 day study period. In contrast, interleukin 6-related gene expression decreased (blue intensity) over the 7 day study period. Conclusions: Critically ill children supplemented with zinc sulfate exhibit a temporal change in global gene expression consistent with restoration of zinc homeostasis and immune function, concomitant with an anti-inflammatory effect. Because we do not have gene expression data on non-supplemented patients, we cannot conclude that the changes are a direct consequence of Zn supplementation. However, these results provide preliminary data to inform a future trial of IV Zn supplementation in critically ill children.Figure