A systematic review and meta-analyses of interleukin-1 receptor associated kinase 3 (IRAK3) action on inflammation in in vivo models for the study of sepsis

BACKGROUND: Interleukin-1 receptor associated kinase 3 (IRAK3) is a critical modulator of inflammation and is associated with endotoxin tolerance and sepsis. Although IRAK3 is known as a negative regulator of inflammation, several studies have reported opposing functions, and the temporal actions of IRAK3 on inflammation remain unclear. A systematic review and meta-analyses were performed to investigate IRAK3 expression and its effects on inflammatory markers (TNF-α and IL-6) after one- or two-challenge interventions, which mimic the hyperinflammatory and immunosuppression phases of sepsis, respectively, using human or animal in vivo models.

METHODS: This systematic review and meta-analyses has been registered in the Open Science Framework (OSF) (Registration DOI: 10.17605/OSF.IO/V39UR). A systematic search was performed to identify in vivo studies reporting outcome measures of expression of IRAK3 and inflammatory markers. Meta-analyses were performed where sufficient data was available.

RESULTS: The search identified 7778 studies for screening. After screening titles, abstracts and full texts, a total of 49 studies were included in the systematic review. The review identified significant increase of IRAK3 mRNA and protein expression at different times in humans compared to rodents following one-challenge, whereas the increases of IL-6 and TNF-α protein expression in humans were similar to rodent in vivo models. Meta-analyses confirmed the inhibitory effect of IRAK3 on TNF-α mRNA and protein expression after two challenges.

CONCLUSIONS: A negative correlation between IRAK3 and TNF-α expression in rodents following two challenges demonstrates the association of IRAK3 in the immunosuppression phase of sepsis. Species differences in underlying biology affect the translatability of immune responses of animal models to human, as shown by the dissimilarity in patterns of IRAK3 mRNA and protein expression between humans and rodents following one challenge that are further influenced by variations in experimental procedures.

Medienart:

E-Artikel

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:17

Enthalten in:

PloS one - 17(2022), 2 vom: 03., Seite e0263968

Sprache:

Englisch

Beteiligte Personen:

Nguyen, Trang H [VerfasserIn]
Turek, Ilona [VerfasserIn]
Meehan-Andrews, Terri [VerfasserIn]
Zacharias, Anita [VerfasserIn]
Irving, Helen R [VerfasserIn]

Links:

Volltext

Themen:

EC 2.7.11.1
IL6 protein, human
IRAK3 protein, human
Interleukin-1 Receptor-Associated Kinases
Interleukin-6
Journal Article
Meta-Analysis
Systematic Review
TNF protein, human
Tumor Necrosis Factor-alpha

Anmerkungen:

Date Completed 24.02.2022

Date Revised 24.02.2022

published: Electronic-eCollection

Citation Status MEDLINE

doi:

10.1371/journal.pone.0263968

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM336996292