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

• 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
• ISSN: 2666-3546; 2666-3546
• DOI: 10.1016/j.bbih.2020.100192

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.