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Updated: Apr 24, 2026
Intravenous Endotoxin Challenge in Healthy Humans: An Experimental Platform to Investigate and Modulate Systemic Inflammation
Published on: May 16, 2016
Recombinant HDL (Milano) protects endotoxin-challenged rats from multiple organ injury and dysfunction
Abstract:
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.
Insights
Apolipoprotein A-IMilano (apoAIM) in reconstituted high-density lipoprotein (rHDLM) effectively combats endotoxemia and multiple organ injury. This enhanced form of apoAIM demonstrates superior anti-inflammatory and antioxidant properties, protecting against severe septic shock.
Area of Science:
- Biochemistry
- Immunology
- Pharmacology
Background:
- Endotoxemia triggers systemic inflammation, leading to septic shock and multiple organ dysfunction syndrome (MODS).
- Apolipoprotein A-IMilano (apoAIM), a cysteine mutant of apoAI, exhibits enhanced cardiovascular protection.
- Reconstituted high-density lipoprotein with apoAIM (rHDLM) may offer therapeutic benefits.
Purpose of the Study:
- To investigate the protective effects of rHDLM against endotoxemia and associated organ injury in rat models.
- To compare the anti-inflammatory and antioxidant efficacy of rHDLM versus wild-type rHDL (rHDLwt).
Main Methods:
- Rats were pretreated with rHDLM or rHDLwt before endotoxin challenge.
- Liver and renal function, lung histopathology, cytokine levels, adhesion molecules, and oxidative stress markers were assessed.
Main Results:
- rHDLM pretreatment significantly attenuated liver and renal dysfunction and lung injury.
- rHDLM suppressed key pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) and ICAM-1.
- rHDLM inhibited lipid peroxidation and enhanced antioxidant capacity more effectively than rHDLwt.
Conclusions:
- rHDLM demonstrates potent anti-inflammatory and antioxidant properties.
- rHDLM offers significant protection against endotoxemia-induced organ injury.
- apoAIM-based rHDL represents a promising therapeutic strategy for sepsis and MODS.
