Apolipoprotein A-I mimetic peptide treatment inhibits inflammatory responses and improves survival in septic rats.
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.
Zhang
Zhenghao
Z
Department of Physiology and Biophysics, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Datta
Geeta
G
Zhang
Yun
Y
Miller
Andrew P
AP
Mochon
Paulina
P
Chen
Yiu-Fai
YF
Chatham
John
J
Anantharamaiah
G M
GM
White
C Roger
CR
D000818:Animals; D016632:Apolipoprotein A-I / Q000276:immunology*; D001794:Blood Pressure / Q000187:drug effects / Q000276:immunology; D001810:Blood Volume / Q000187:drug effects / Q000276:immunology; D004452:Echocardiography; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D015850:Interleukin-6 / Q000097:blood; D008075:Lipoproteins, HDL / Q000097:blood; D008297:Male; D018716:Molecular Mimicry / Q000276:immunology; D010455:Peptides / Q000276:immunology / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy / Q000276:immunology / Q000401:mortality; D013318:Stroke Volume / Q000187:drug effects / Q000276:immunology; D016277:Ventricular Function, Left / Q000187:drug effects* / Q000276:immunology*
D016632:Apolipoprotein A-I; D015850:Interleukin-6; D008075:Lipoproteins, HDL; D010455:Peptides