PROTECTIVE EFFECTS OF RECONSTITUTED HIGH-DENSITY-LIPOPROTEIN IN RABBIT GRAM-NEGATIVE BACTEREMIA MODELS

Reconstituted high-density lipoproteins (rHDLs) have the ability to bi nd bacterial lipopolysaccharide and to reduce its endotoxin activity i n vitro and in vivo, The aim of the present studies was to investigate the therapeutic potential of rHDL in bacteremia models, Gram-negative sepsis was induced in anaesthetized rabbits by intravenous infusion o f Escherichia coli organisms (4 x 10(9) CFU/kg infused over 2 hours) a nd treated with appropriate antibiotics, rHDL or placebo was infused e ither before (prophylaxis) or 1 hour after (therapy) the beginning of the bacterial challenge, In the control groups, the bacterial challeng e resulted in transient bacteremia, high plasma levels of lipopolysacc haride, secretion of TNF, and symptoms of sepsis, including hypotensio n and acidosis, rHDL had no influence on blood bacterial counts; howev er, plasma lipopolysaccharide levels were significantly reduced, Peak plasma TNF concentrations were reduced after prophylactic but not afte r therapeutic rHDL administration, Both prophylactic and therapeutic r HDL improved clinical outcome: acidosis was significantly attenuated a nd blood pressure tended to be higher in the rHDL groups, No effects o f rHDL were seen in a similar model of gram-positive sepsis induced by the infusion of Staphylococcus aureus.