An Indirect Co-culturing Model System That Links Lithium Anti-inflammatory Effects and Endothelial Integrity in RVFV Inoculated Raw 264.7 Cells

Rift Valley fever virus (RVFV) is a mosquito born zoonotic viral infection that has resulted in a number of outbreaks in Africa and Arabian Peninsula. RVFV elicits flue like symptoms and clinical complications such as haemorrhagic fever, however, the link between this viral infection and haemorrhagic fever is not well elucidated. Viral haemorrhagic fever is characterised by altered endothelial integrity from damaged endothelial cells that results in septic shock and multiple organ failure leading to death. Therefore, this study hypothesises the use of lithium as prophylaxis for oxidative stress-linked endothelial leakage post-RVFV infection. Co-inoculation model system was used to measure the effects of inflammatory mediators on endothelial integrity. The xCelligence system together with the Transwell assay were used to measure endothelial integrity. Results from the xCelligence system showed that endothelial cells exposed to RVFV-infected, lithium-treated Raw 264.7 cells supernatant showed a cell integrity index of above 4.0, displaying similar protective properties as compared to RVFV-inoculated Raw 264.7 cells supernatant not treated with lithium. Moreover, lithium-treated cells supernatant upregulated the expression of Adherence junction genes. The endothelial integrity observed in the permeability assays correlates with the expression of the molecules involved in keeping the cell-to-cell junction intact. Thus, this study links the anti-inflammatory properties of lithium with cytoprotective ability of endothelial integrity.