Endotoxemia, the systemic inflammatory host response to
infection, leads to severe
septic shock and multiple organ injury and dysfunction syndrome (
MOPS), which cause mortality.
Apolipoprotein A-IMilano (apoAIM), a naturally occurring
cysteine mutant of apoAI with dimers as its effective form, showed an enhanced cardiovascular protective activity compared with wild-type apoAI (apoAIwt). To investigate the role of recombinant
high-density lipoprotein (rHDL) reconstituted with apoAIM (rHDLM) on
endotoxemia and
MOPS, we examined the anti-inflammatory,
anti-oxidant, and protective effects of this
cysteine mutant against organ injury in
endotoxin-challenged rat models compared with rHDLwt. In the present study, we demonstrated for the first time that pretreatment with rHDLM significantly attenuated liver and renal dysfunction and histopathological features of
lung injury in
endotoxin-challenged
endotoxemia rats. Administration of rHDLM to
endotoxemia rats dramatically suppressed proinflammatory
cytokines and adhesion molecule increase in
tumor necrosis factor α,
interleukin 1β,
interleukin 6, and
intercellular adhesion molecule 1. In addition, rHDLM pretreatment inhibited lipid peroxidation and enhanced total
antioxidant capacity in vivo. In comparison with rHDLwt, rHDLM showed enhanced capacity on anti-inflammatory and
anti-oxidant functions. In summary, administration of rHDLM protected
endotoxin-challenged
endotoxemia and
MOPS through enhanced anti-inflammatory and
anti-oxidant properties.