Citrulline supplementation exacerbates sepsis severity in infected preterm piglets via early induced immunosuppression
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Citrulline supplementation exacerbates sepsis severity in infected preterm piglets via early induced immunosuppression. / Zhong, Jingren; Johansen, Sebastian Høj; Bæk, Ole; Nguyen, Duc Ninh.
I: Journal of Nutritional Biochemistry, Bind 131, 109674, 2024.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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 -
ID: 394530154