Lipopolysaccharide (LPS) contributes importantly to morbidity and mortality in
sepsis. Bovine intestinal
alkaline phosphatase (
BIAP) was demonstrated to detoxify LPS through dephosphorylation. LPS injection combined with
BIAP reduced
inflammation and improved survival in various experimental settings. In this study, single-dose
intravenous administration of
BIAP (0.15 IU/g) was applied in a murine cecal
ligation and
puncture (CLP) model of polymicrobial
sepsis. Saline was given as control (S group). Treatment with
BIAP prior to CLP (prophylaxis;
BIAP-P group) or shortly after (early treatment;
BIAP-ET group) reduced
cytokine concentrations in plasma and peritoneal lavage fluid (PLF).
Tumor necrosis factor-alpha peak levels decreased from 170 pg/ml (S) to 57.5 (
BIAP-P) and 82.5 (
BIAP-ET) in plasma and in PLF from 57.5 pg/ml (S) to 35.3 (
BIAP-P) and 16.8 (
BIAP-ET) (all, P < 0.05). Peak
interleukin-6 levels in plasma decreased from 19.3 ng/ml (S) to 3.4 (
BIAP-P) and 11.5 (
BIAP-ET) and in PLF from 32.6 ng/ml (S) to 13.4 (
BIAP-P) and 10.9 (
BIAP-ET) (all, P < 0.05). Macrophage
chemoattractant protein 1 peak levels in plasma decreased from 2.0 ng/ml (S) to 1.0 (
BIAP-P) and 0.7 (
BIAP-ET) and in PLF from 6.4 (S) to 2.3 (
BIAP-P) and 1.3 ng/ml (
BIAP-ET) (all, P < 0.05).
BIAP-treated groups showed decreased
transaminase activity in plasma and decreased
myeloperoxidase activity in the lung, indicating reduced associated hepatocellular and pulmonary damage. Survival was not significantly altered by
BIAP in this single-dose regimen. In polymicrobial
secondary peritonitis, both prophylactic and early
BIAP treatment attenuates the inflammatory response both locally and systemically and reduces associated liver and lung damage.