Experimental procedure: Thirty six virgin adult female rats (n = 6) were randomly divided into six groups; Group 1-3 were normal control (NC), Sham (SHAM) and ovariectomized group (OVX) respectively whereas group 4-6 were PPD rats forced-fed once daily with distilled water (PPD), fish oil (PPD + FO; 9 g/kg) and Fluoxetine (PPD + FLX; 15 mg/kg) respectively from postpartum day 1 and continued for 10 consecutive days. Rats behaviors were evaluated on postpartum day 10 through open field test (OFT) and forced swimming test (FST), followed by biochemical analysis of NLRP3 inflammasome proteins pathway in their brain and determination of neutrophil to lymphocyte ratio (NLR).
Results: PPD-induced rats exhibited high immobility and low swimming time in FST with increased inflammatory status; NLR, IL-1β and NFкB/NLRP3/caspase-1 activity in their hippocampus. However, administration of FO or fluoxetine reversed the aforementioned abnormalities.
Conclusion: In conclusion, 10 days supplementation with FO ameliorated the depressive-like behaviors in PPD rats by targeting the NFкB/NLRP3/caspase-1/IL-1β activity. This has shed light on the potential of NLRP3 as a therapeutic target in treatment of PPD in rats.
METHODS: Plasmodium berghei infection in male ICR mice was used as the rodent model of choice. The time course of IL-35 expression in the systemic circulation and tissues of P. berghei infected mice as well as their healthy control counterparts was assessed by enzyme linked immunosorbent assay and immunohistochemistry respectively. The effect of modulating IL-35 by recombinant IL-35 protein or neutralizing anti-Epstein-Barr virus-induced gene 3 antibody on the cytokine environment during P. berghei infection was assessed by flow cytometry. Furthermore, the influence of modulating IL-35 on histopathological hallmarks of malaria and disease progression was evaluated.
RESULTS: Interleukin-35 was significantly up regulated in serum and tissues of P. berghei infected mice and correlated with parasitaemia. Neutralization of IL-35 significantly enhanced the release of IFN-γ, decreased the expression of IL-6 and decreased parasitaemia patency. Neutralization of IL-35 was also associated with a tendency towards increased survival as well as the absence of pathological features associated with malaria infection unlike recombinant IL-35 protein administration which sustained a normal course of infection and unfavourable malaria associated histological outcomes in P. berghei infected mice.
CONCLUSION: These results indicate the involvement of IL-35 in P. berghei induced malaria infection. IL-35 neutralization strategies may represent viable therapeutic modalities beneficial for the resolution of malaria infection.