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