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Table 3 Overview of studies demonstrating a detoxifying role of AP in vivo

From: Endotoxin- and ATP-neutralizing activity of alkaline phosphatase as a strategy to limit neuroinflammation

Model Duration of model Inducing agent or adjuvant Treatment regime Result Reference
Acute myocardial infarction in BALB/c mice 24 hours None (coronary artery ligation) BIAP, 5 U i.v. prophylactic Reduction of IL-6 and MCP-1 by 40%, IL-1β reduced by 30%. No effect on IL-10 Fiechter et al., submitted
Colitis in C57BL/6 mice 12 days Dextran sulphate sodium (DSS) BIAP orally, 100 U/day starting four days after disease induction Reduction in body weight loss and TNF-α. Reduced gut leukocyte infiltration and tissue damage [18]
Sepsis and lethal E. coli infection in BALB/c mice 24 hours Live E. coli i.p. Human placental AP, 1.5 U i.v. Reduction in mortality. [26]
LPS toxicity in mice and piglets 24 and 72 hours Live E. coli i.p. in mice or LPS i.v. in piglets (200 ng/kg bodyweight) BIAP i.v., 1.5 U in mice or 3.000 U in piglets Increased survival in mice from 20% to 80%. Reduction in TNF-α by 98% in piglets. No toxicity of BIAP 4000 U/day for 28 days [16]
Liver ischemia-reperfusion in rats 24 hours None (clamping of hepatic blood vessels) BIAP single dose i.v. 0.5 U/g bodyweight Decreased neutrophil influx and tissue damage [27]
Secondary peritonitis in C57BL/6 mice 72 hours Endogenous gut microbiota (due to cecal ligation puncture) BIAP single dose 0.15 U/g bodyweight Reduced inflammation and hepatocellular and pulmonary damage [28]
Septic shock in sheep 30 hours Feces injection i.p. BIAP bolus 60 U/kg and continuous infusion 20 U/kg/h for 15h Reduced IL-6, improved gas exchange and longer survival [29]
MOG35-55 induced EAE in C57BL/6 mice 28 days Complete Freund’s adjuvant and pertussis toxin Presymptomatic BIAP, 5 U/day i.p. for 7 days Reduced clinical signs, reduced T-cell proliferation to immunogen Huizinga et al. (this study)
  1. BIAP, bovine intestinal alkaline phosphatase. LPS, lipopolysaccharide; TNFα, tumor necrosis factor α.