Apolipoprotein A-I mimetic peptide treatment inhibits inflammatory responses and improves survival in septic rats.

Academic Article

Abstract

  • Systemic inflammation induces a multiple organ dysfunction syndrome that contributes to morbidity and mortality in septic patients. Since increasing plasma apolipoprotein A-I (apoA-I) and HDL may reduce the complications of sepsis, we tested the hypothesis that the apoA-I mimetic peptide 4F confers similar protective effects in rats undergoing cecal ligation and puncture (CLP) injury. Male Sprague-Dawley rats were randomized to undergo CLP or sham surgery. IL-6 levels were significantly elevated in plasma by 6 h after CLP surgery compared with shams. In subsequent studies, CLP rats were further subdivided to receive vehicle or 4F (10 mg/kg) by intraperitoneal injection, 6 h after sepsis induction. Sham-operated rats received saline. Echocardiographic studies showed a reduction in left ventricular end-diastolic volume, stroke volume, and cardiac output (CO) 24 h after CLP surgery. These changes were associated with reduced blood volume and left ventricular filling pressure. 4F treatment improved blood volume status, increased CO, and reduced plasma IL-6 in CLP rats. Total cholesterol (TC) and HDL were 79 +/- 5 and 61 +/- 4 mg/dl, respectively, in sham rats. TC was significantly reduced in CLP rats (54 +/- 3 mg/dl) due to a reduction in HDL (26 +/- 3 mg/dl). 4F administration to CLP rats attenuated the reduction in TC (69 +/- 4 mg/dl) and HDL (41 +/- 3 mg/dl) and prevented sepsis-induced changes in HDL protein composition. Increased plasma HDL in 4F-treated CLP rats was associated with an improvement in CO and reduced mortality. It is proposed that protective effects of 4F are related to its ability to prevent the sepsis-induced reduction in plasma HDL.
  • Keywords

  • Animals, Apolipoprotein A-I, Blood Pressure, Blood Volume, Echocardiography, Inflammation, Interleukin-6, Lipoproteins, HDL, Male, Molecular Mimicry, Peptides, Rats, Rats, Sprague-Dawley, Sepsis, Stroke Volume, Ventricular Function, Left
  • Digital Object Identifier (doi)

    Authorlist

  • Zhang Z; Datta G; Zhang Y; Miller AP; Mochon P; Chen Y-F; Chatham J; Anantharamaiah GM; White CR
  • Start Page

  • H866
  • End Page

  • H873
  • Volume

  • 297
  • Issue

  • 2