| Title: |
A Neonatal Murine Escherichia coli Sepsis Model Demonstrates That Adjunctive Pentoxifylline Enhances the Ratio of Anti- vs. Pro-inflammatory Cytokines in Blood and Organ Tissues |
| Authors: |
Esther M. Speer, Elizabet Diago-Navarro, Lukasz S. Ozog, Mahnoor Raheel, Ofer Levy, Bettina C. Fries |
| Source: |
Frontiers in Immunology, Vol 11 (2020) |
| Publisher Information: |
Frontiers Media S.A., 2020. |
| Publication Year: |
2020 |
| Collection: |
LCC:Immunologic diseases. Allergy |
| Subject Terms: |
newborn, sepsis, Escherichia coli, anti-inflammatory, pentoxifylline, interleukin 10, Immunologic diseases. Allergy, RC581-607 |
| More Details: |
Introduction: Neonatal sepsis triggers an inflammatory response that contributes to mortality and multiple organ injury. Pentoxifylline (PTX), a phosphodiesterase inhibitor which suppresses pro-inflammatory cytokines, is a candidate adjunctive therapy for newborn sepsis. We hypothesized that administration of PTX in addition to antibiotics decreases live bacteria-induced pro-inflammatory and/or enhances anti-inflammatory cytokine production in septic neonatal mice without augmenting bacterial growth.Methods: Newborn C57BL/6J mice (< 24 h old) were injected intravenously with 105 colony forming units (CFUs)/g weight of a bioluminescent derivative of the encapsulated clinical isolate Escherichia coli O18:K1. Adequacy of intravenous injections was validated using in vivo bioluminescence imaging and Evans blue. Pups were treated with gentamicin (GENT), PTX, (GENT + PTX) or saline at 0, 1.5, or 4 h after sepsis initiation, and euthanized after an additional 4 h. CFUs and cytokines were measured from blood and homogenized organ tissues.Results: GENT alone inhibited bacterial growth, IL-1β, and IL-6 production in blood and organs. Addition of PTX to GENT profoundly inhibited E. coli-induced TNF and enhanced IL-10 in blood of newborn mice at all timepoints, whereas it primarily upregulated IL-10 production in peripheral organs (lung, spleen, brain). PTX, whether alone or adjunctive to GENT, did not increase microbial colony counts in blood and organs.Conclusion: Addition of PTX to antibiotics in murine neonatal E. coli sepsis promoted an anti-inflammatory milieu through inhibition of plasma TNF and enhancement of IL-10 production in plasma and organs without increasing bacterial growth, supporting its utility as a potential adjunctive agent for newborn sepsis. |
| Document Type: |
article |
| File Description: |
electronic resource |
| Language: |
English |
| ISSN: |
1664-3224 |
| Relation: |
https://www.frontiersin.org/article/10.3389/fimmu.2020.577878/full; https://doaj.org/toc/1664-3224 |
| DOI: |
10.3389/fimmu.2020.577878 |
| Access URL: |
https://doaj.org/article/1d1e849025ad4ae58935abd260aed09f |
| Accession Number: |
edsdoj.1d1e849025ad4ae58935abd260aed09f |
| Database: |
Directory of Open Access Journals |
