Fig 1: hep-SPLEVs inhibit various forms of inflammation.(A) Survival curves of mice treated with PBS (n = 9), hep-EVs (n = 8), or hep-SPLEVs (n = 8) in the moderate to severe sepsis model. (B) qPCR evaluation of splenic Il6 and Tnf expression in mice treated for 10 days with hep-EVs or hep-SPLEVs after cecum puncture. (C) Survival curves after treatment with PBS, hep-EVs, or hep-SPLEVs (n = 9 for each) in the LPS-induced coagulopathy model. (D) Serum ALT and AST levels with or without administration of hep-SPLEVs at 48 hours in the CCl4-induced hepatitis model (n = 3 to 4). (E to G) Compared effects of hep-SPLEVs (n = 9) and hep-EVs (n = 6) as DSS alone (n = 10) in DSS-challenged mice. Each mice treated 7 days. (E) Representative photos of colon of mice (left). Decrease in colon length (%) after treatments (right). (F) H&E staining of the colon in mice. Black arrowheads show inflammatory cells, white arrowhead shows loss of intestinal structure, double-headed arrow shows thinning, and black arrow shows edema. Scale bar, 100 μm. (G) Inflammatory and DAI scores in mouse colon. (H) H&E staining of mouse lungs with or without H3 influenza infection for 7 days in the presence or absence of hep-SPLEVs (left). Lung injury scores in these mice [naïve (n = 3), influenza (n = 4), and influenza + hep-SPLEVs (n = 5)] are shown (right). (I) Viral titers as monitored by qPCR of the H3 influenza gene in the lungs in (H) [naïve (n = 9), influenza (n = 9), and influenza + hep-SPLEVs (n = 13)]. N-terminally His-tagged sPLA2-Xbv was used under the condition shown in table S3. *P < 0.033, **P < 0.002, ***P < 0.001, and ****P < 0.0001.