PMID- 38504987
OWN - NLM
STAT- MEDLINE
DCOM- 20240321
LR  - 20240409
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 15
DP  - 2024
TI  - Causal associations between circulating cytokines and risk of sepsis and related 
      outcomes: a two-sample Mendelian randomization study.
PG  - 1336586
LID - 10.3389/fimmu.2024.1336586 [doi]
LID - 1336586
AB  - INTRODUCTION: Sepsis represents a critical medical condition that arises due to 
      an imbalanced host reaction to infection. Central to its pathophysiology are 
      cytokines. However, observational investigations that explore the 
      interrelationships between circulating cytokines and susceptibility to sepsis 
      frequently encounter challenges pertaining to confounding variables and reverse 
      causality. METHODS: To elucidate the potential causal impact of cytokines on the 
      risk of sepsis, we conducted two-sample Mendelian randomization (MR) analyses. 
      Genetic instruments tied to circulating cytokine concentrations were sourced from 
      genome-wide association studies encompassing 8,293 Finnish participants. We then 
      evaluated their links with sepsis and related outcomes using summary-level data 
      acquired from the UK Biobank, a vast multicenter cohort study involving over 
      500,000 European participants. Specifically, our data spanned 11,643 sepsis cases 
      and 474,841 controls, with subsets including specific age groups, 28-day 
      mortality, and ICU-related outcomes. RESULTS AND DISCUSSION: MR insights 
      intimated that reduced genetically-predicted interleukin-10 (IL-10) levels 
      causally correlated with a heightened sepsis risk (odds ratio [OR] 0.68, 95% 
      confidence interval [CI] 0.52-0.90, P=0.006). An inverse relationship emerged 
      between monocyte chemoattractant protein-1 (MCP-1) and sepsis-induced mortality. 
      Conversely, elevated macrophage inflammatory protein 1 beta (MIP1B) 
      concentrations were positively linked with both sepsis incidence and associated 
      mortality. These revelations underscore the causal impact of certain circulating 
      cytokines on sepsis susceptibility and its prognosis, hinting at the therapeutic 
      potential of modulating these cytokine levels. Additional research is essential 
      to corroborate these connections.
CI  - Copyright (c) 2024 Zhi, Ma, Ji, Bao and Li.
FAU - Zhi, Feng
AU  - Zhi F
AD  - Department of Critical Care Medicine, Wuxi No.2 People's Hospital, Jiangnan 
      University Medical Center, Wuxi, China.
FAU - Ma, Jia-Wei
AU  - Ma JW
AD  - Department of Critical Care Medicine, Wuxi No.2 People's Hospital, Jiangnan 
      University Medical Center, Wuxi, China.
AD  - Department of Critical Care Medicine, Aheqi County People's Hospital, Xinjiang, 
      China.
FAU - Ji, Dan-Dan
AU  - Ji DD
AD  - Department of Critical Care Medicine, Wuxi No.2 People's Hospital, Jiangnan 
      University Medical Center, Wuxi, China.
FAU - Bao, Jie
AU  - Bao J
AD  - Department of Critical Care Medicine, Wuxi No.2 People's Hospital, Jiangnan 
      University Medical Center, Wuxi, China.
FAU - Li, Qian-Qian
AU  - Li QQ
AD  - Department of Critical Care Medicine, Wuxi No.2 People's Hospital, Jiangnan 
      University Medical Center, Wuxi, China.
LA  - eng
PT  - Journal Article
PT  - Multicenter Study
PT  - Research Support, Non-U.S. Gov't
DEP - 20240305
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Cytokines)
SB  - IM
MH  - Humans
MH  - *Cytokines
MH  - Cohort Studies
MH  - Genome-Wide Association Study
MH  - Mendelian Randomization Analysis
MH  - *Sepsis/genetics
PMC - PMC10948396
OTO - NOTNLM
OT  - Mendelian randomization
OT  - circulating cytokines
OT  - macrophage inflammatory protein 1 beta
OT  - monocyte chemoattractant protein-1
OT  - sepsis
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2024/03/20 06:46
MHDA- 2024/03/21 12:43
PMCR- 2024/01/01
CRDT- 2024/03/20 04:02
PHST- 2023/11/11 00:00 [received]
PHST- 2024/02/21 00:00 [accepted]
PHST- 2024/03/21 12:43 [medline]
PHST- 2024/03/20 06:46 [pubmed]
PHST- 2024/03/20 04:02 [entrez]
PHST- 2024/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2024.1336586 [doi]
PST - epublish
SO  - Front Immunol. 2024 Mar 5;15:1336586. doi: 10.3389/fimmu.2024.1336586. 
      eCollection 2024.