Enteral Administration of a Synthetic Monoacetyldiglyceride Improves Survival in a Murine Model of Abdominal Sepsis

Abstract

A monoacetyldiglyceride (MADG) markedly improves survival in a murine model of abdominal sepsis. MADGs have been shown to stimulate hematopoiesis in vitro. We examined effects of MADG administration in setting of cecal ligation and puncture (CLP) and hypothesized that oral (p.o.) administration of MADG would result in alterations of cytokine and chemokine expression after CLP.

Four groups of 20 mice: sham group underwent celiotomy but not CLP; control group underwent CLP and administration of phosphate buffer solution; simultaneous treatment group had administration of 50 mg/kg MADG p.o. Immediately, before CLP and at 24, 48, and 72-hour post-CLP, posttreatment group had initial administration of MADG at 1-hour post-CLP, and at 24, 48, and 72-hour postoperative. We followed survival to 10-day postoperative. Serum and tissue levels of pro- and anti-inflammatory cytokines were measured. Serum levels of chemokines stromal cell-derived factor (SDF-1) and stem cell factor (SCF) were measured to ascertain if effects of MADG involve stimulation of bone marrow stromal and stem cells. Polymerase chain reaction was used to measure SDF and SCF mRNA expression in liver and lung.

Administration of MADG (p.o.) significantly improved survival in mice after CLP with associated systemic alterations of a variety of cytokines. Increased levels of mRNA coding for SCF and SDF in lung and liver were found after CLP.

Administration of MADG (p.o.) after CLP results in marked improvement in survival. Cytokine level changes demonstrate associated immunomodulatory effects. These effects may be mediated by bone marrow stromal and stem cell activation, evidenced by increases in SDF and SCF. Further study of behavior of bone marrow-derived stem cells in setting of sepsis is warranted. MADG may hold promise for use in treatment of sepsis.