We thank Dr. Fujita and colleagues for their useful comments about our article. Indeed, we performed two different types of experiments. We first studied the neutralization of lipopolysaccharide (LPS) by high-density lipoprotein (HDL). The aim of that first experiment was to compare LPS tissue distribution and the effects of HDL on this tissue distribution independently of tumor necrosis factor-alpha production. We used FITC-LPS at 0.17 mg/kg, that is, the same dose as previously used for the study of LPS clearance in normal rat. 1 In the second protocol, LPS was used at a dose which may induce tumor necrosis factor-alpha hyperproduction in cirrhotic rats, that is 0.5 mg/kg.
Dr. Fujita asked why serum HDL levels increased during invasive experiments under anesthesia. In control rats, HDL levels did not significantly rise after the experiment (0.46 versus Ͻ0.44 g/L). In our cirrhotic rats, plasma HDL levels rose from 0.25 Ϯ 0.09 to 0.47 Ϯ 0.02 g/L (mean, standard error of the mean), but this value was not statistically significant (P ϭ 0.11).
The authors wonder why we administered reconstituted HDL (rHDL) before LPS challenge. This is a pertinent issue. As underlined in the discussion of our article, the best way to study the potential curative effects of rHDL would be to administer rHDL after LPS injection, as Fujita et al. previously did with ApoA1 intraperitoneal administration. 2 However, we aimed to study the possible preventive action of rHDL. Indeed, we know well that in patients with cirrhosis without infection, serum bacterial DNA can be found in ascitic fluid, 3 suggesting a "preinfected state" and a potential beneficial effect of rHDL even before infection.
We agree with the authors that testing different doses of HDL is necessary to determine the optimal dosage requested in cirrhotic rats. However, we chose the dosage of 80 mg/kg because it was that used in previous studies after LPS exposure in rats infected with E. coli-derived LPS, and that Gram-negative infections are the most common infections in patients with cirrhosis.