Table 1.
Experimental high-density lipoprotein (HDL) therapies in animals models of sepsis and their outcomes.
| HDL | Dose and administration | Sepsis model | Main findings | Reference |
|---|---|---|---|---|
| 18A:Egg PC (1:2 wt/wt) sHDL |
80 mg/kg; prophylactic tail vein IV infusion | Swiss Webster mice; LPS (salmonella) 10 mg/kg; IP injection; within 15 min of HDL |
Three–fourfold increase in 48-h survival rate vs control (p < 0.05) | Levine et al., 1993 |
| L-4F Peptide | 25 mg/kg, IP, concurrently with lipopolysaccharide (LPS) | Sprague-Dawley rats; 10 mg/kg LPS; IP injection | Reduction in VCAM-1 expression in excised aortae | Gupta et al., 2005 |
| 4F Peptide | 10 mg/kg; IP injection post-LPS challenge | Sprague-Dawley rats; LPS 10 mg/kg or 30 mg/kg; IP injection | 10 mg/kg LPS: 4F slowed LPS plasma clearance; reduced hypotension at 6 h; 30 mg/kg LPS: 4F increased plasma HDL levels; increased 24-h survival |
Dai et al., 2010 |
| 4F Peptide | 10 mg/kg, IP, 6 h post-CLP | Sprague-Dawley rats; CLP | Reduced IL-6; restored CO, right atrial pressure, and plasma volume; improved 2-day survival rate; reversed sepsis-induced changes in lipoprotein profile | Zhang et al., 2009 |
| 4F Peptide | 10 mg/kg; IP injection 6 h post-cecal ligation and puncture (CLP) | Wistar Rats; CLP | Restored renal, hepatic, and cardiac functions; reduced renal tubule damage; restored expression levels of Slit2, Robo4, and eNOS; increased plasma HDL; improved 4-day survival; no change in MAP | Moreira et al., 2014 |
| D-4F Peptide | 20 μg daily for 9 days; IP injection | C57BL/6J mice; nasally innoculated with 105 PFU influenza virus A/WSN/33 | Prevented lymphoid hyperplasia; increased PON activity; prevented drop in core body temperature; suppressed plasma IL-6 levels; increased plasma HDL and inhibited lipoprotein alteration; reduced viral titers by >50% at all time points | Van Lenten et al., 2002 |
| ApoA1 | 10 mg/kg; IP injection 1 h post-LPS challenge | Wistar rats; LPS 1 mg/kg (TNF analysis) or 5 mg/kg (survival study); IP injection | Reduced plasma TNF-α levels in rats given 1 mg/kg LPS; increased 5-day survival rate from 0 to 90% in rats given 5 mg/kg LPS | Imai et al., 2003 |
| ApoA1, human plasma purified | 100 mg/kg; IV infusion post-LPS challenge | Balb/c mice; LPS 5 mg/kg; IP injection | Increased both survival rate and average survival time over 3 days | Yan et al., 2006 |
| ApoA1 Milano ApoA1:Soy PC (1:3.35 mol/mol) rHDL |
40 mg/kg; prophylactic IV injection | Wistar rats; 400 EU/kg Gram-negative bacterial endotoxin; IV injection | Increase in HDL-C; improved renal and hepatic function; inhibition of cytokines TNF-α, IL-1β, IL-6; reduced expression of ICAM-1 | Zhang et al., 2015 |
| ApoA1:Soy PC (1:200 mol/mol) rHDL |
75 mg/kg ApoA1; prophylactic continuous IV infusion over 25 min | NZW rabbits; LPS 25 μg/kg continuous IV infusion over 6 h; start 20 min post-rHDL treatment | Complete inhibition of TNF-α; prevented LPS-induced hypotension; reduced metabolic acidosis; no significant effect on serum LPS levels | Hubsch et al., 1993 |
| ApoA1:Egg PC (1:2 w/w) rHDL |
500 mg/kg ApoA1; IV infusion at 0.1 g/kg/hr; split into three doses: 0.3, 0.1, and 0.1 g/kg administered at 0.5, 8, and 16 h post-infection, respectively | 2-year old Beagles surgically implanted with E. coli-infected fibrin clot | Reduced plasma endotoxin levels; decreased plasma TNF-α; decreased liver function; decreased 2-day survival and average survival time | Quezado et al., 1995 |
| CSL-111 ApoA1:Soy PC (1:150 mol/mol) rHDL |
75 mg/kg ApoA1; (a) Prophylactic IV infusion over 40 min (b) Treatment by IV infusion over 20 min, 1 h post-bacterial challenge |
NZW Rabbits (1) Gram (-) Sepsis: 4 × 109 CFU/kg E. coli; IV infusion over 2 h (2) Gram (+) Sepsis: 2 × 109 CFU/kg; IV infusion over 2 h |
(1 a) Prophylactic rHDL: reduced plasma LPS and TNF-α; reduction in metabolic acidosis; no effect on hypotension or blood bacterial levels (1 b) rHDL Treatment: reduction in LPS after 4 h; reduced metabolic acidosis and creatinine; no effect on blood bacterial counts or TNF-α; no effect on hypotension (2) No effect in Gram (+) sepsis |
Hubsch et al., 1995 |
| CSL-111 ApoA1:Soy PC (1:150 mol/mol) rHDL |
25 or 50 mg/kg ApoA1; Prophylactic IV infusion over 40 min | NZW rabbits; LPS 10 μg/kg; continuous IV infusion over 2 h; start 15 min post-rHDL completion | Reduced TNF-α levels and increased TNF-α clearance for both rHDL doses; rHDL 50 mg/kg reduced hypotension at t = 3–4 h; no effect on plasma LPS levels; no effect on blood leukocyte count | Casas et al., 1995 |
| CSL-111 ApoA1:Soy PC (1:150 mol/mol) rHDL |
40 mg/kg; prophylactic IV infusion over 4 h | Healthy male volunteers (20–28 years); Endotoxin 4 ng/kg IV bolus; given 3.5 h post-rHDL start | Elevated HDL levels; reduced endotoxin-induced clinical symptoms, i.e., chills, myalgia, backache, nausea, and vomiting; reduced plasma cytokine levels of TNF-α, IL-6, and IL-8; inhibited early leukopenia, monopenia, and neutropenia; reduced monocyte CD14 expression | Pajkrt et al., 1996 |