TY - JOUR

T1 - Citrulline supplementation exacerbates sepsis severity in infected preterm piglets via early induced immunosuppression

AU - Zhong, Jingren

AU - Johansen, Sebastian Høj

AU - Bæk, Ole

AU - Nguyen, Duc Ninh

N1 - Publisher Copyright: © 2024 The Author(s)

PY - 2024

Y1 - 2024

N2 - Arginine (ARG)/Citrulline (CIT) deficiency is associated with increased sepsis severity after infection. Supplementation of CIT to susceptible patients with ARG/CIT deficiency such as preterm newborns with suspected infection might prevent sepsis, via maintaining immune and vascular function. Caesarean-delivered, parenterally nourished preterm pigs were treated with CIT (1g/kg bodyweight) via oral or continuous intravenous supplementation, then inoculated with live Staphylococcus epidermidis and clinically monitored for 14 h. Blood, liver, and spleen samples were collected for analysis. In vitro cord blood stimulation was performed to explore how CIT and ARG affect premature blood cell responses. After infection, oral CIT supplementation led to higher mortality, increased blood bacterial load, and systemic and hepatic inflammation. Intravenous CIT administration showed increased inflammation and bacterial burdens without significantly affecting mortality. Liver transcriptomics and data from in vitro blood stimulation indicated that CIT induces systemic immunosuppression in preterm newborns, which may impair resistance response to bacteria at the early stage of infection, subsequently causing later uncontrollable inflammation and tissue damage. The early stage of CIT supplementation exacerbates sepsis severity in infected preterm pigs, likely via inducing systemic immunosuppression.

AB - Arginine (ARG)/Citrulline (CIT) deficiency is associated with increased sepsis severity after infection. Supplementation of CIT to susceptible patients with ARG/CIT deficiency such as preterm newborns with suspected infection might prevent sepsis, via maintaining immune and vascular function. Caesarean-delivered, parenterally nourished preterm pigs were treated with CIT (1g/kg bodyweight) via oral or continuous intravenous supplementation, then inoculated with live Staphylococcus epidermidis and clinically monitored for 14 h. Blood, liver, and spleen samples were collected for analysis. In vitro cord blood stimulation was performed to explore how CIT and ARG affect premature blood cell responses. After infection, oral CIT supplementation led to higher mortality, increased blood bacterial load, and systemic and hepatic inflammation. Intravenous CIT administration showed increased inflammation and bacterial burdens without significantly affecting mortality. Liver transcriptomics and data from in vitro blood stimulation indicated that CIT induces systemic immunosuppression in preterm newborns, which may impair resistance response to bacteria at the early stage of infection, subsequently causing later uncontrollable inflammation and tissue damage. The early stage of CIT supplementation exacerbates sepsis severity in infected preterm pigs, likely via inducing systemic immunosuppression.

KW - Arginine

KW - Citrulline

KW - Infection

KW - Innate immunity

KW - Newborn

KW - Preterm

U2 - 10.1016/j.jnutbio.2024.109674

DO - 10.1016/j.jnutbio.2024.109674

M3 - Journal article

C2 - 38825026

AN - SCOPUS:85195172110

VL - 131

JO - Journal of Nutritional Biochemistry

JF - Journal of Nutritional Biochemistry

SN - 0955-2863

M1 - 109674

ER -