Fig. 6.

Attenuation of inflammation exacerbation via temporally or spatially controlled LPS and modmRNA-LNP administrations. Pro-inflammatory cytokines of interleukin-6 (IL-6) in serum (a, b) and macrophage inflammatory protein (MIP-2) in liver homogenate (c) of either naïve or LPS-treated mice under different treatment regimens. LPS at 2 mg kg⁻¹, and modmRNA-LNP, anti-PECAM modmRNA-LNP, or anti-PlVAP modmRNA-LNP at 0.32 mg-mRNA kg⁻¹ were administered via retro-orbital intravenous injection. Results shown in (a) are obtained from the timepoint study in which mice were first administered with either LPS or mRNA-LNP, then respectively treated with modmRNA-LNP or LPS at the same time (modmRNA-LNP + LPS + 0 h), t = 1 h (modmRNA-LNP/LPS-1 h, in which LPS was administered 1 h post-mRNA-LNP treatment, or LPS/modmRNA-LNP + 1 h, in which LPS was administered 1 h before modmRNA-LNP treatment), t= 4 h (LPS/modmRNA-LNP + 4 h, in which LPS was administered 4 h before modmRNA-LNP treatment), or t = 24 h (LPS/modmRNA-LNP + 24 h, in which LPS was administered 24 h before modmRNA-LNP treatment). Each column represents Mean ± SEM. Group size is 3 animals. Statistical analysis was performed by one-way ANOVA with Bonferroni correction, comparing LPS/modmRNA-LNP to either LPS/modmRNA-LNP + 24 h, LPS/anti-PECAM modmRNA-LNP, or LPS/anti-PLVAP modmRNA-LNP (*P < 0.05, **P < 0.01, and ***P < 0.001).