Immune and metabolic responses in early and late sepsis during mild dietary zinc restriction

• Published in: The Journal of surgical research Vol. 210; pp. 47 - 58
• Main Authors: Crowell, Kristen T., MD, Phillips, Brett E., PhD, Kelleher, Shannon L., PhD, Soybel, David I., MD, Lang, Charles H., PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2017
• Subjects: Animals; Biomarkers - metabolism; Blotting, Western; Cytokines; Cytokines - metabolism; Hepatic protein synthesis; Inflammatory response; Liver - metabolism; Male; Mice; Mice, Inbred C57BL; Random Allocation; Sepsis; Sepsis - immunology; Sepsis - metabolism; Surgery; Zinc - deficiency; Keratinocyte chemoattractant/human growth-regulated oncogene; CLP; Interleukin; S6-kinase 1; inflammatory response; 4E-binding protein 1; Zinc deficiency; KC-GRO; IFN-γ; Tumor necrosis factor alpha; mammalian target of rapamycin; Zn; Zinc adequate; Mild zinc deficient; mTOR; cytokines; Nuclear magnetic resonance; IL; Janus kinase-signal transducer and activators of transcription; JAK-STAT; ZA; Zinc; S6K1; Marginally dietary zinc deprivation; Serum amyloid A; NMR; SAA; ZM; TNF-α; MZD; 4E-BP1; hepatic protein synthesis; Cecal ligation and puncture; sepsis; Interferon gamma; Sepsis; Inflammatory response; Cytokines; Hepatic protein synthesis
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2016.10.020

Abstract Background Mild dietary zinc (Zn) deficiency is wide-spread in human populations, but its influence on recovery following acute illness is poorly understood. In a mouse model of abdominal sepsis (cecal-ligation-puncture, CLP), systemic immune responses and liver metabolism were monitored in early (24 hr) and late (5 day) phases, under control conditions and during mild dietary Zn restriction. Methods Mice were fed diets adequate (ZA) or marginally deficient (ZM) in zinc (30 vs 10 mg zinc/kg diet) for 4 weeks, before undergoing laparotomy alone (nonseptic control) or CLP (septic). Results Among nonseptic mice, the ZM state was not associated with differences in inflammation or metabolic responses. Among septic mice, mortality did not differ between the ZA and ZM groups. In the early phase, the ZM state amplified increases in plasma IL-6, TNF-α and IL-10, while dampening the IFN-γ response. In the late phase, subtle but significant ZM-associated increases were observed in plasma IL-5 and IFN-γ levels, and hepatic protein synthesis, the latter of which appeared to be mTOR-independent and was associated with increased hepatic TNF-α mRNA content. Conclusions Without increasing mortality, the ZM state is associated with a more disordered acute systemic inflammatory response and persistence or enhancement of acute phase responses within the liver parenchyma.