Does the Antisecretory Peptide AF-16 modulate fluid balance and inflammation in experimental peritonitis induced sepsis?

Abstract

Sepsis is a life-threatening condition due to a dysregulated immunological response to infection. Apart from source control and broad-spectrum antibiotics, management is based on fluid resuscitation and vasoactive drugs. Fluid resuscitation implicates the risk of volume overload, which in turn is associated with longer stay in intensive care, prolonged use of mechanical ventilation and increased mortality. Antisecretory factor (AF), an endogenous protein, is detectable in most tissues and in plasma. The biologically active site of the protein is located in an 8-peptide sequence, contained in a synthetic 16-peptide fragment, named AF-16. The protein as well as the peptide AF-16 has multiple modulatory effects on abnormal fluid transport and edema formation/resolution as well as in a variety of inflammatory conditions. Apart from its anti-secretory and anti-inflammatory characteristics, AF is an inhibitor of capillary leakage in intestine. It is not known whether the protein AF or the peptide AF-16 can ameliorate symptoms in sepsis. We hypothesized that AF-16 decreases the degree of hemodynamic instability, the need of fluid resuscitation, vasopressor dose and tissue edema in fecal peritonitis. To test the hypothesis, we induced peritonitis and sepsis by injecting autologous fecal solution into abdominal cavity of anesthetized pigs, and randomized (in a blind manner) the animals to intervention (AF-16, n=8) or control (saline, n=8) group. After onset of hemodynamic instability (defined as mean arterial pressure 5 minutes), resuscitation was initiated by an infusion of AF-16 or saline. We recorded respiratory and hemodynamic parameters hourly for twenty hours and collected post mortem tissue samples at the end of the experiment. No differences between the groups were observed regarding hemodynamics, fluid balance, lung mechanics, gas exchange or histology. This experimental study suggests that AF-16 does not modulate sepsis symptoms in peritonitis induced sepsis.