Objective: To determine the anti-inflammatory functions of different cysteine mutants of apolipoprotein A-I recombinant HDLs.
Methods: The authors reconstituted recombinant HDLs (namely rHDL74, rHDL129, rHDL195 and rHDL228) by mixing wild type or those mutants with dipalmitoyl phosphatidylcholine and examined their in vivo effects upon LPS-induced endotoxemia in mice.
Results: At 24 h post-injection, mice receiving rHDL74 [TNF-alpha: (24 +/- 3) pg/ml; IL-1beta: (45 +/- 5) pg/ml] had a significant decrease of plasma tumor necrosis factor alpha (TNF-alpha) and interleukin-1beta (IL-1beta) as compared with control mice receiving either saline or rHDLwt [TNF-alpha: (135 +/- 12) pg/ml; IL-1beta: (82 +/- 8) pg/ml, P < 0.05]. Administration of rHDL74 to mice injected with LPS also led to a protection of lung against acute injury and attenuation of endotoxin-induced clinical symptoms in mice as compared with controls injected with LPS only.
Conclusion: Compared with rHDLwt, rHDL74 exhibits higher anti-inflammation capabilities. And it may be a potential clinical candidate for therapy for endotoxin-induced septic shock.