Variability in PolyIC induced immune response: Implications for preclinical maternal immune activation models

Abstract

Maternal infection during pregnancy may increase the risk of offspring neurodevelopmental disorders. The preclinical Polyinosinic-polycytidylic acid (PolyIC) model has become one of the most widely used approaches in maternal immune activation (MIA) research. However, variability in molecular weight may impact the immune activating potential of PolyIC. Nulliparous rats injected with high molecular weight PolyIC exhibit pronounced cytokine response and sickness behavior that was not observed in rats injected low molecular weight PolyIC. Although an essential next step is to extend these studies to pregnant animals, the preliminary results suggest that PolyIC molecular weight is an important experimental design consideration.

Keywords: Cytokine; Immune; Maternal immune activation; PolyIC; Polyinosinic-polycytidylic acid; Sickness behavior.

Fig. 1.

IL-6 Response following PolyIC Injection. Only animals that received HMW-PolyIC demonstrate elevated IL-6 levels compared to saline controls 3 h and 6 h after the injection. * P < 0.05.

Fig. 2.

Expanded cytokine profiles of TNFα, IFN-γ, IL-1β, at 3 h and 6 h post PolyIC injection. (A) At 3 h post injection animals that received either LMW- or HMW-PolyIC demonstrated elevated TNFα levels compared to saline controls. The HMW-PolyIC injected animals continue to demonstrate higher TNFα levels than controls 6 h post injection. (B) For IFN-γ, only the HMW-injected animals differed from controls at both 3 h and 6 h post injection. (C) At 3 h and 6 h post injection animals that received HMW-PolyIC demonstrated elevated IL-1β levels compared to saline controls. LMW-PolyIC injected animals differed from controls at 3 h, but not 6 h post injection.

Fig. 3.

Rat receiving LMW-PolyIC showed no significant differences compared with rats receiving saline alone. However, rats receiving HMW-PolyIC showed significant differences in (A) weight loss (B) CO2 production, (C) O2 consumption, (D) Food intake and (D) Water intake compared with rats receiving saline. * P < 0.05.