recAP administration ameliorates sepsis outcomes through modulation of gut and liver inflammation.

Abstract

Sepsis, broadly described as a systemic infection, is one of the leading causes of death and long-term disability worldwide. There are limited therapeutic options available that either improve survival and/or improve the quality of life in survivors. Ilofotase alfa, also known as recombinant alkaline phosphatase (recAP), has been associated with reduced mortality in a subset of patients with sepsis-associated acute kidney injury. However, whether recAP exhibits any therapeutic benefits in other organ systems beyond the kidney is less clear. The objective of this study was to evaluate the effects of recAP on survival, behavior, and intestinal inflammation in a mouse model of sepsis, cecal ligation and puncture (CLP). Following CLP, either recAP or saline vehicle was administered via daily intraperitoneal injections to determine its treatment efficacy from early through late sepsis. We found that administration of recAP suppressed indices of inflammation in the gut and liver but did not improve survival or behavioral outcomes. These results demonstrate that recAP's therapeutic efficacy in the gut and liver may provide a valuable treatment to improve long-term outcomes in sepsis survivors.