Effect of Negative Pressure Therapy on the Inflammatory Response of the Intestinal Microenvironment in a Porcine Septic Model.

Kenneth C Norbury,Mary Pat Moyer

doi:10.1155/2015/419841

Abstract

In a swine model of ischemia/reperfusion injury coupled with sepsis, we have previously shown attenuation of secondary organ injury and decreased mortality with negative pressure therapy (NPT). We hypothesized that NPT modulates the intestinal microenvironment by mediating the innate immune system. Sepsis was induced in 12 anesthetized female pigs. Group 1 (n = 6) was decompressed at 12 hrs after injury (T 12) and treated with standard of care (SOC), and group 2 (n = 6) with NPT for up to T 48. Immunoparalysis was evident as lymphocytopenia at T 24 in both groups; however, survival was improved in the NPT group versus SOC (Odds ratio = 4.0). The SOC group showed significant reduction in lymphocyte numbers compared to NPT group by T 48 (p < 0.05). The capacity of peritoneal fluid to stimulate a robust reactive oxygen species response in vitro was greater for the NPT group, peaking at T 24 for both M1 (p = 0.0197) and M2 macrophages (p = 0.085). Plasma elicited little if any effect which was confirmed by microarray analysis. In this septic swine model NPT appeared to modulate the intestinal microenvironment, facilitating an early robust, yet transient, host defense mediated by M1 and M2 macrophages. NPT may help overcome immunoparalysis that occurs during inflammatory response to septic injury.

Highlights

Sepsis carries a high mortality rate and is the leading cause of death in critically ill patients [1,2,3]
To determine possible inflammatory mediators and available tools, we extensively reviewed the literature and made choices based on the following factors: (a) prior validation of the monocyte-like and neutrophillike cell line models by several investigators; (b) commercial availability of cells and reagents and their established use for this type of research; and (c) the desire to develop humanbased cell test systems that will provide robust, reproducible readouts to better allow interstudy comparisons and statistical analyses
The Odds ratio occurring in the negative pressure therapy (NPT) group compared to the standard of care (SOC) group was 4.0, indicating that survival was 4 times higher in the NPT group than in the SOC group

Summary

Introduction

Sepsis carries a high mortality rate and is the leading cause of death in critically ill patients [1,2,3]. Two independent septic disorders have been identified: “septic shock,” a highly lethal syndrome caused by cardiovascular collapse within 24– 48 hours of onset, and “severe sepsis,” a more protracted condition associated with organ dysfunction that progresses more slowly over 7–14 days with a mortality rate of 30–70% [4]. Upon recognition of a possible pathogen, resident macrophages within tissues initiate an early inflammation response that leads to recruitment of cells of the innate immune system, namely, neutrophils and monocytes [6], and to production of inflammatory cytokines, including interleukin (IL-1β), tumor necrosis factor (TNF), and high mobility group B protein-1 (HMGB1) [7]. Specific mediators and overt production of nitric oxide and reactive oxygen species (ROS) are key molecular mechanisms in the processes that can lead to tissue injury, including acute vascular and lung responses

Methods

Results

Conclusion