Figure 6.

rhPLTP retained its protective effects in WT mice with polymicrobial sepsis. WT mice received iv injections of vehicle (control) or rhPLTP (25 µg in a volume of 200 µl) 2 h, 4 h, 7 h and 23 h after CLP. (A) Repeated iv injections of rhPLTP after CLP induced a significant increase in plasma PLTP activity 24 h after CLP. PLTP activity was measured in plasma before, 8 h and 24 h after CLP and expressed as a percentage of T0 mouse plasma activity (n = 12–14 mice per group, Kruskal-Wallis test with Dunn’s multiple comparisons test). (B) Repeated iv injections of rhPLTP increased mouse survival after CLP. Numbers of alive and dead animals were compared using the χ² test (n = 14–15 mice per group). (C) Repeated iv injections of rhPLTP prevented the production of cytokines (IL-6, MCP-1, TNF-α, IL-1β, IL-10) after CLP. Plasma samples, harvested from WT mice before CLP, 8 h and 24 h after CLP, were assayed using a Milliplex mouse cytokine panel (n = 12–14 mice per group, Mann-Whitney test). (D and E) Intravenous rhPLTP administration reduced bacterial burdens in blood and peritoneal lavages of WT mice with polymicrobial sepsis. Colony-forming units (CFU) were determined in blood samples (D) before CLP, 8 h and 24 h following CLP and in peritoneal lavage fluids (E) 24 h after CLP (n = 12–14 mice per group, Mann-Whitney test). (F) Intravenous rhPLTP administration significantly reduced LPS levels in WT plasma after CLP. LPS concentrations were determined by direct quantitation of 3-hydroxymyristate (3HM) over a 24 h period following CLP in plasma from WT mice (n = 12–14 mice per group, Mann-Whitney test). Data are means ± sem. *P < 0.05, **P  < 0.01.