Burns, inflammation, and intestinal injury: protective effects of an anti-inflammatory resuscitation strategy. J Trauma 2009 Dec;67(6):1162-8
Date
12/17/2009Pubmed ID
20009662Pubmed Central ID
PMC4251580DOI
10.1097/TA.0b013e3181ba3577Scopus ID
2-s2.0-73949099877 (requires institutional sign-in at Scopus site) 41 CitationsAbstract
BACKGROUND: Intestinal barrier breakdown after severe burn can lead to intestinal inflammation, which may act as the source of the systemic inflammatory response. In vitro intestinal cell studies have shown that mitogen-activated protein kinase (MAPK) signaling is an important modulator of intestinal inflammation. We have previously observed that pentoxifylline (PTX) attenuates burn-induced intestinal permeability and tight junction breakdown. We hypothesized that PTX would limit intestinal barrier breakdown and attenuate inflammatory signaling via the MAPK pathway.
METHODS: Male balb/c mice underwent 30% total body surface area full-thickness steam burn. Immediately after burn, animals received an intraperitoneal injection of PTX (12.5 mg/kg) in normal saline or normal saline alone. In vivo intestinal permeability to 4 kDa fluorescein isothiocyanate-dextran was measured. Intestinal extracts were obtained to measure interleukin-6 by enzyme-linked immunosorbent assay, and phosphorylated p38 MAPK, p38 MAPK, phosphorylated extracellular signal-related kinase (1/2) (ERK (1/2)), and ERK (1/2) by immunoblotting. Acute lung injury was assessed by histology at 24 hours after burn.
RESULTS: Administration of PTX immediately after injury attenuated burn-induced intestinal permeability. PTX also decreased the burn-induced phosphorylation of p38 MAPK and decreased phosphorylation of ERK (1/2) at 2 hours and 24 hours after injury. Animals given PTX had decreased intestinal interleukin-6 levels. A single dose of PTX also decreased histologic lung injury at 24 hours after burn.
CONCLUSION: PTX attenuates burn-induced intestinal permeability and subsequent intestinal inflammation. Use of PTX after burn was also associated with decreased acute lung injury. Because of its compelling anti-inflammatory effects, PTX may be an ideal candidate for use as an immunomodulatory adjunct to resuscitation fluid.
Author List
Costantini TW, Peterson CY, Kroll L, Loomis WH, Putnam JG, Wolf P, Eliceiri BP, Baird A, Bansal V, Coimbra RAuthor
Carrie Peterson MD, MS, FACS, FASCRS Associate Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBurns
Inflammation
Intestinal Absorption
Intestinal Mucosa
Intestines
Male
Mice
Mice, Inbred BALB C
Pentoxifylline
Permeability
Phosphorylation
Resuscitation
Treatment Outcome
p38 Mitogen-Activated Protein Kinases
