The poly(I:C)-induced maternal immune activation model; a systematic review and meta-analysis of cytokine levels in the offspring

The poly(I:C)-induced maternal immune activation model; a systematic review and meta-analysis of cytokine levels in the offspring

The maternal polyinosinic:polycytidylic acid (poly(I:C)) animal model is frequently used to study how maternal immune activation may impact neuro development in the offspring. Here, we present the first systematic review and meta-analysis on the effects of maternal poly(I:C) injection on immune medi...

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Published in:Brain, behavior, & immunity. Health Vol. 11; p. 100192
Main Authors: Hameete, Bart C., Fernández-Calleja, José M.S., de Groot, Martje W.G.D.M., Oppewal, Titia Rixt, Tiemessen, Machteld M., Hogenkamp, Astrid, de Vries, Rob B.M., Groenink, Lucianne
Format: Journal Article
Language:English
Published: Elsevier Inc 01-02-2021
Elsevier
Subjects:
Cytokines
Immune system
Maternal exposure
Maternal immune activation
Meta-analysis
Models animal
Neurodevelopmental disorders
Poly I–C
Review
Systematic review
Models animal
Maternal immune activation
Cytokines
Maternal exposure
Systematic review
Poly I–C
Neurodevelopmental disorders
Meta-analysis
Immune system
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Abstract The maternal polyinosinic:polycytidylic acid (poly(I:C)) animal model is frequently used to study how maternal immune activation may impact neuro development in the offspring. Here, we present the first systematic review and meta-analysis on the effects of maternal poly(I:C) injection on immune mediators in the offspring and provide an openly accessible systematic map of the data including methodological characteristics. Pubmed and EMBASE were searched for relevant publications, yielding 45 unique papers that met inclusion criteria. We extracted data on immune outcomes and methodological characteristics, and assessed the risk of bias. The descriptive summary showed that most studies reported an absence of effect, with an equal number of studies reporting an increase or decrease in the immune mediator being studied. Meta-analysis showed increased IL-6 concentrations in the offspring of poly(I:C) exposed mothers. This effect appeared larger prenatally than post-weaning. Furthermore, poly(I:C) administration during mid-gestation was associated with higher IL-6 concentrations in the offspring. Maternal poly(I:C) induced changes in IL-1β, Il-10 and TNF-α concentrations were small and could not be associated with age of offspring, gestational period or sampling location. Finally, quality of reporting of potential measures to minimize bias was low, which stresses the importance of adherence to publication guidelines. Since neurodevelopmental disorders in humans tend to be associated with lifelong changes in cytokine concentrations, the absence of these effects as identified in this systematic review may suggest that combining the model with other etiological factors in future studies may provide further insight in the mechanisms through which maternal immune activation affects neurodevelopment. •Long-term effects of maternal poly(I:C) on immune mediators in the offspring appear limited.•Prenatal measurements and mid gestation poly(I:C) injection are associated with increases in IL-6 concentrations.•Variety in methodological conduct hampers identification of key elements that affect cytokine concentrations.•The quality of reporting of potential measures to minimize bias is poor.
AbstractList The maternal polyinosinic:polycytidylic acid (poly(I:C)) animal model is frequently used to study how maternal immune activation may impact neuro development in the offspring. Here, we present the first systematic review and meta-analysis on the effects of maternal poly(I:C) injection on immune mediators in the offspring and provide an openly accessible systematic map of the data including methodological characteristics. Pubmed and EMBASE were searched for relevant publications, yielding 45 unique papers that met inclusion criteria. We extracted data on immune outcomes and methodological characteristics, and assessed the risk of bias. The descriptive summary showed that most studies reported an absence of effect, with an equal number of studies reporting an increase or decrease in the immune mediator being studied. Meta-analysis showed increased IL-6 concentrations in the offspring of poly(I:C) exposed mothers. This effect appeared larger prenatally than post-weaning. Furthermore, poly(I:C) administration during mid-gestation was associated with higher IL-6 concentrations in the offspring. Maternal poly(I:C) induced changes in IL-1β, Il-10 and TNF-α concentrations were small and could not be associated with age of offspring, gestational period or sampling location. Finally, quality of reporting of potential measures to minimize bias was low, which stresses the importance of adherence to publication guidelines. Since neurodevelopmental disorders in humans tend to be associated with lifelong changes in cytokine concentrations, the absence of these effects as identified in this systematic review may suggest that combining the model with other etiological factors in future studies may provide further insight in the mechanisms through which maternal immune activation affects neurodevelopment. •Long-term effects of maternal poly(I:C) on immune mediators in the offspring appear limited.•Prenatal measurements and mid gestation poly(I:C) injection are associated with increases in IL-6 concentrations.•Variety in methodological conduct hampers identification of key elements that affect cytokine concentrations.•The quality of reporting of potential measures to minimize bias is poor.
The maternal polyinosinic:polycytidylic acid (poly(I:C)) animal model is frequently used to study how maternal immune activation may impact neuro development in the offspring. Here, we present the first systematic review and meta-analysis on the effects of maternal poly(I:C) injection on immune mediators in the offspring and provide an openly accessible systematic map of the data including methodological characteristics.Pubmed and EMBASE were searched for relevant publications, yielding 45 unique papers that met inclusion criteria. We extracted data on immune outcomes and methodological characteristics, and assessed the risk of bias. The descriptive summary showed that most studies reported an absence of effect, with an equal number of studies reporting an increase or decrease in the immune mediator being studied.Meta-analysis showed increased IL-6 concentrations in the offspring of poly(I:C) exposed mothers. This effect appeared larger prenatally than post-weaning. Furthermore, poly(I:C) administration during mid-gestation was associated with higher IL-6 concentrations in the offspring. Maternal poly(I:C) induced changes in IL-1β, Il-10 and TNF-α concentrations were small and could not be associated with age of offspring, gestational period or sampling location. Finally, quality of reporting of potential measures to minimize bias was low, which stresses the importance of adherence to publication guidelines.Since neurodevelopmental disorders in humans tend to be associated with lifelong changes in cytokine concentrations, the absence of these effects as identified in this systematic review may suggest that combining the model with other etiological factors in future studies may provide further insight in the mechanisms through which maternal immune activation affects neurodevelopment.
The maternal polyinosinic:polycytidylic acid (poly(I:C)) animal model is frequently used to study how maternal immune activation may impact neuro development in the offspring. Here, we present the first systematic review and meta-analysis on the effects of maternal poly(I:C) injection on immune mediators in the offspring and provide an openly accessible systematic map of the data including methodological characteristics. Pubmed and EMBASE were searched for relevant publications, yielding 45 unique papers that met inclusion criteria. We extracted data on immune outcomes and methodological characteristics, and assessed the risk of bias. The descriptive summary showed that most studies reported an absence of effect, with an equal number of studies reporting an increase or decrease in the immune mediator being studied. Meta-analysis showed increased IL-6 concentrations in the offspring of poly(I:C) exposed mothers. This effect appeared larger prenatally than post-weaning. Furthermore, poly(I:C) administration during mid-gestation was associated with higher IL-6 concentrations in the offspring. Maternal poly(I:C) induced changes in IL-1β, Il-10 and TNF-α concentrations were small and could not be associated with age of offspring, gestational period or sampling location. Finally, quality of reporting of potential measures to minimize bias was low, which stresses the importance of adherence to publication guidelines. Since neurodevelopmental disorders in humans tend to be associated with lifelong changes in cytokine concentrations, the absence of these effects as identified in this systematic review may suggest that combining the model with other etiological factors in future studies may provide further insight in the mechanisms through which maternal immune activation affects neurodevelopment. • Long-term effects of maternal poly(I:C) on immune mediators in the offspring appear limited. • Prenatal measurements and mid gestation poly(I:C) injection are associated with increases in IL-6 concentrations. • Variety in methodological conduct hampers identification of key elements that affect cytokine concentrations. • The quality of reporting of potential measures to minimize bias is poor.
ArticleNumber 100192
Author Hameete, Bart C.
Tiemessen, Machteld M.
Groenink, Lucianne
Fernández-Calleja, José M.S.
Hogenkamp, Astrid
de Vries, Rob B.M.
de Groot, Martje W.G.D.M.
Oppewal, Titia Rixt
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  organization: Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, Utrecht, 3584 CG, the Netherlands
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  givenname: José M.S.
  surname: Fernández-Calleja
  fullname: Fernández-Calleja, José M.S.
  email: j.m.s.fernandezcalleja@uu.nl
  organization: Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, Utrecht, 3584 CG, the Netherlands
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  givenname: Martje W.G.D.M.
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  givenname: Machteld M.
  surname: Tiemessen
  fullname: Tiemessen, Machteld M.
  email: machteld.tiemessen@nutricia.com
  organization: Research & Innovation, GCoE Immunology, Danone Nutricia Research, Uppsalalaan 12, Utrecht, 3584 CT, the Netherlands
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  givenname: Astrid
  orcidid: 0000-0003-2051-9259
  surname: Hogenkamp
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  organization: Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, Utrecht, 3584 CG, the Netherlands
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  givenname: Rob B.M.
  surname: de Vries
  fullname: de Vries, Rob B.M.
  email: rob.devries@radboudumc.nl
  organization: SYstematic Review Center for Laboratory (Animal) Experimentation, Department for Health Evidence, Radboud University Medical Center, Geert Grooteplein zuid 10, Nijmegen, 6525 GA, the Netherlands
– sequence: 8
  givenname: Lucianne
  surname: Groenink
  fullname: Groenink, Lucianne
  email: l.groenink@uu.nl
  organization: Department of Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, Universiteitsweg 99, Utrecht, 3584 CG, the Netherlands
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Keywords Models animal
Maternal immune activation
Cytokines
Maternal exposure
Systematic review
Poly I–C
Neurodevelopmental disorders
Meta-analysis
Immune system
Language English
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Snippet The maternal polyinosinic:polycytidylic acid (poly(I:C)) animal model is frequently used to study how maternal immune activation may impact neuro development...
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SubjectTerms Cytokines
Immune system
Maternal exposure
Maternal immune activation
Meta-analysis
Models animal
Neurodevelopmental disorders
Poly I–C
Review
Systematic review
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Title The poly(I:C)-induced maternal immune activation model; a systematic review and meta-analysis of cytokine levels in the offspring
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