PMID- 36615909
OWN - NLM
STAT- MEDLINE
DCOM- 20230110
LR  - 20230308
IS  - 2072-6643 (Electronic)
IS  - 2072-6643 (Linking)
VI  - 15
IP  - 1
DP  - 2023 Jan 3
TI  - Ex Vivo Evaluation of Glutamine Treatment in Sepsis and Trauma in a Human 
      Peripheral Blood Mononuclear Cells Model.
LID - 10.3390/nu15010252 [doi]
LID - 252
AB  - We aimed to assess the lipopolysaccharide (LPS), or heat shock (HS) induction, 
      and glutamine-modulating effects on heat shock protein-90alpha (HSP90alpha) and cytokines 
      in an ex vivo model using peripheral blood mononuclear cells (PBMCs). The PBMCs 
      of patients with septic shock, trauma-related systemic inflammatory response 
      syndrome (SIRS), and healthy subjects were incubated with 1 mug/mL LPS at 43  degrees C 
      (HS). Glutamine 10 mM was added 1 hour before or after induction or not at all. 
      We measured mRNA HSP90alpha, monocyte (m) and lymphocyte (l) HSP90alpha proteins, 
      interleukin (IL)-1b, -6, -8, -10, tumor necrosis factor-alpha (TNF-alpha), and monocyte 
      chemoattractant protein-1 (MCP-1) supernatant levels. Heat shock increased the 
      HSP90alpha mRNA and mHSP90alpha in all groups (10-fold in sepsis, p < 0.001 and p = 
      0.047, respectively). LPS induced the mHSP90alpha and lHSP90alpha in healthy (p < 0.001) 
      and mHSP90alpha in SIRS (p = 0.004) but not in sepsis. LPS induced the cytokines at 
      24 and 48 h in all groups, especially in trauma (p < 0.001); HS only induced the 
      IL-8 in healthy (p = 0.003) and septic subjects (p = 0.05). Glutamine at 10 mM 
      before or after stimulation did not alter any induction effect of LPS or HS on 
      HSP90alpha mRNA and mHSP90alpha protein in sepsis. In SIRS, glutamine before LPS 
      decreased the mHSP90alpha but increased it when given after HS (p = 0.018). Before or 
      after LPS (p = 0.049) and before HS (p = 0.018), glutamine decreased the lHSP90alpha 
      expression in sepsis but increased it in SIRS when given after HS (p = 0.003). 
      Regarding cytokines, glutamine enhanced the LPS-induced MCP-1 at 48 h in healthy 
      (p = 0.011), SIRS (p < 0.001), and sepsis (p = 0.006). In conclusion, glutamine 
      at 10 mM, before or after LPS and HS, modulates mHSP90alpha and lHSP90alpha in sepsis and 
      SIRS differently and unpredictably. Although it does not alter the stimulation 
      effect on interleukins, glutamine enhances the LPS induction effect on 
      supernatant MCP-1 in all groups. Future research should seek to elucidate better 
      the impact of glutamine and temperature modulation on HSP90alpha and MCP-1 pathways 
      in sepsis and trauma.
FAU - Briassouli, Efrossini
AU  - Briassouli E
AUID- ORCID: 0000-0002-9766-8968
AD  - Department of Immunology-Histocompatibility, Specialized Center & Referral Center 
      for Primary Immunodeficiencies-Paediatric Immunology, "Aghia Sophia" Children's 
      Hospital, 11527 Athens, Greece.
AD  - First Department of Propaedeutic Medicine, School of Medicine, National and 
      Kapodistrian University of Athens (NKUA), 11527 Athens, Greece.
AD  - Infectious Diseases Department "MAKKA", "Aghia Sophia" Children's Hospital, First 
      Department of Paediatrics, School of Medicine, National and Kapodistrian 
      University of Athens (NKUA), 11527 Athens, Greece.
FAU - Tzanoudaki, Marianna
AU  - Tzanoudaki M
AUID- ORCID: 0000-0001-9630-142X
AD  - Department of Immunology-Histocompatibility, Specialized Center & Referral Center 
      for Primary Immunodeficiencies-Paediatric Immunology, "Aghia Sophia" Children's 
      Hospital, 11527 Athens, Greece.
FAU - Goukos, Dimitris
AU  - Goukos D
AD  - First Department of Propaedeutic Medicine, School of Medicine, National and 
      Kapodistrian University of Athens (NKUA), 11527 Athens, Greece.
FAU - Vardas, Kostas
AU  - Vardas K
AD  - First Critical Care Department, Evangelismos Hospital, School of Medicine, 
      National and Kapodistrian University of Athens (NKUA), 15772 Athens, Greece.
FAU - Briassoulis, Panagiotis
AU  - Briassoulis P
AUID- ORCID: 0000-0002-9789-9002
AD  - Attikon University Hospital, School of Medicine, National and Kapodistrian 
      University of Athens (NKUA), 12462 Athens, Greece.
AD  - Pediatric Intensive Care Unit, University Hospital, School of Medicine, 
      University of Crete, 71110 Heraklion, Greece.
FAU - Ilia, Stavroula
AU  - Ilia S
AUID- ORCID: 0000-0002-0936-368X
AD  - Pediatric Intensive Care Unit, University Hospital, School of Medicine, 
      University of Crete, 71110 Heraklion, Greece.
AD  - Postgraduate Program "Emergency and Intensive Care in Children Adolescents and 
      Young Adults", School of Medicine, University of Crete, 71003 Heraklion, Greece.
FAU - Kanariou, Maria
AU  - Kanariou M
AD  - Department of Immunology-Histocompatibility, Specialized Center & Referral Center 
      for Primary Immunodeficiencies-Paediatric Immunology, "Aghia Sophia" Children's 
      Hospital, 11527 Athens, Greece.
FAU - Routsi, Christina
AU  - Routsi C
AD  - First Critical Care Department, Evangelismos Hospital, School of Medicine, 
      National and Kapodistrian University of Athens (NKUA), 15772 Athens, Greece.
FAU - Nanas, Serafim
AU  - Nanas S
AD  - First Critical Care Department, Evangelismos Hospital, School of Medicine, 
      National and Kapodistrian University of Athens (NKUA), 15772 Athens, Greece.
FAU - Daikos, George L
AU  - Daikos GL
AD  - First Department of Propaedeutic Medicine, School of Medicine, National and 
      Kapodistrian University of Athens (NKUA), 11527 Athens, Greece.
FAU - Briassoulis, George
AU  - Briassoulis G
AUID- ORCID: 0000-0003-0928-6183
AD  - Pediatric Intensive Care Unit, University Hospital, School of Medicine, 
      University of Crete, 71110 Heraklion, Greece.
AD  - Postgraduate Program "Emergency and Intensive Care in Children Adolescents and 
      Young Adults", School of Medicine, University of Crete, 71003 Heraklion, Greece.
LA  - eng
GR  - European Union (European Social Fund (ESF)/
GR  - Operational Program "Education and Lifelong Learning" of the National Strategic 
      Reference Framework (NSRF) Research Funding Program, THALES/
PT  - Journal Article
DEP - 20230103
PL  - Switzerland
TA  - Nutrients
JT  - Nutrients
JID - 101521595
RN  - 0RH81L854J (Glutamine)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Cytokines)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Interleukins)
RN  - 0 (Heat-Shock Proteins)
RN  - 0 (RNA, Messenger)
SB  - IM
MH  - Humans
MH  - *Leukocytes, Mononuclear/metabolism
MH  - Glutamine/pharmacology/metabolism
MH  - Lipopolysaccharides/pharmacology
MH  - *Sepsis/metabolism
MH  - Systemic Inflammatory Response Syndrome
MH  - Cytokines/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Interleukins/metabolism
MH  - Heat-Shock Proteins/metabolism
MH  - RNA, Messenger/metabolism
PMC - PMC9824313
OTO - NOTNLM
OT  - MCP-1
OT  - critically ill
OT  - cytokines
OT  - flow cytometry
OT  - glutamine
OT  - heat shock
OT  - heat shock protein
OT  - interleukin
OT  - lipopolysaccharide
OT  - mRNA
OT  - peripheral blood mononuclear cells
OT  - sepsis
OT  - trauma
COIS- The authors declare no conflict of interest.
EDAT- 2023/01/09 06:00
MHDA- 2023/01/11 06:00
PMCR- 2023/01/03
CRDT- 2023/01/08 01:37
PHST- 2022/11/29 00:00 [received]
PHST- 2022/12/21 00:00 [revised]
PHST- 2022/12/29 00:00 [accepted]
PHST- 2023/01/08 01:37 [entrez]
PHST- 2023/01/09 06:00 [pubmed]
PHST- 2023/01/11 06:00 [medline]
PHST- 2023/01/03 00:00 [pmc-release]
AID - nu15010252 [pii]
AID - nutrients-15-00252 [pii]
AID - 10.3390/nu15010252 [doi]
PST - epublish
SO  - Nutrients. 2023 Jan 3;15(1):252. doi: 10.3390/nu15010252.