Protective effect of rhBNP on intestinal injury in the canine models of sepsis

Sepsis is the leading cause of death in the intensive care units worldwide. Proinflammatory cytokines such as TNF (tumor necrosis factor)-α and IL (interleukin)-6 mediate the pathogenesis of septic shock characterized by hemodynamic instability and end-stage multi-organ functional failure. Brain natriuretic peptide (BNP) has been used as a diagnostic and prognostic biomarker in the cardiovascular disorders. Most recently, plasma level of BNP has also been used to predict outcomes of critical illnesses including sepsis. We have recently reported that human recombinant BNP (rhBNP) could protect lungs from acute proinflammatory injury in response to LPS-injection. In the current study, using LPS (lipopolysaccharide)-induced canine sepsis models, we further investigated the effect of rhBNP on intestinal injury and its potential mechanisms. We have found that rhBNP (5 μg or 10 μg/kg weight) could significantly reduce intestinal tissue damage in response to LPS-injection in the dog sepsis models through down-regulating proinflammatory cytokines TNF-α and IL-6 (5–10 fold decrease compared to LPS-injection only group) by a mechanism of suppressing IκB phosphorylation and NF-κB expression. These findings suggest that BNP protect intestinal tissues from endotoxin-induced hyper-inflammatory injury and thus, may be used as therapeutic agents for sepsis.