Anti-inflammatory response is associated with mortality and severity of infection in sepsis

Alix Ashare; Linda S Powers; Noah S Butler; Kevin C Doerschug; Martha M Monick; Gary W Hunninghake

doi:10.1152/ajplung.00231.2004

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Anti-inflammatory response is associated with mortality and severity of infection in sepsis

Journal article

Open access

Peer reviewed

Anti-inflammatory response is associated with mortality and severity of infection in sepsis

Alix Ashare, Linda S Powers, Noah S Butler, Kevin C Doerschug, Martha M Monick and Gary W Hunninghake

American journal of physiology. Lung cellular and molecular physiology, Vol.288(4), pp.L633-640

04/2005

DOI: 10.1152/ajplung.00231.2004

PMID: 15579629

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Abstract

Using a murine model of sepsis, we found that the balance of tissue pro- to anti-inflammatory cytokines directly correlated with severity of infection and mortality. Sepsis was induced in C57BL/6 mice by cecal ligation and puncture (CLP). Liver tissue was analyzed for levels of IL-1beta, IL-1 receptor antagonist (IL-1ra), tumor necrosis factor (TNF)-alpha, and soluble TNF receptor 1 by ELISA. Bacterial DNA was measured using quantitative real-time PCR. After CLP, early predominance of proinflammatory cytokines (6 h) transitioned to anti-inflammatory predominance at 24 h. The elevated anti-inflammatory cytokines were mirrored by increased tissue bacterial levels. The degree of anti-inflammatory response compared with proinflammatory response correlated with the bacterial concentration. To modulate the timing of the anti-inflammatory response, mice were treated with IL-1ra before CLP. This resulted in decreased proinflammatory cytokines, earlier bacterial load, and increased mortality. These studies show that the initial tissue proinflammatory response to sepsis is followed by an anti-inflammatory response. The anti-inflammatory phase is associated with increased bacterial load and mortality. These data suggest that it is the timing and magnitude of the anti-inflammatory response that predicts severity of infection in a murine model of sepsis.

Tumor Necrosis Factor-alpha - metabolism

Interleukin-1 - genetics

Sialoglycoproteins - genetics

Sialoglycoproteins - metabolism

Tumor Necrosis Factor-alpha - genetics

Receptors, Tumor Necrosis Factor, Type I - metabolism

RNA, Messenger - metabolism

Ligation

RNA, Bacterial - genetics

Female

RNA, Bacterial - metabolism

Interleukin-1 - metabolism

Sepsis - immunology

Enzyme-Linked Immunosorbent Assay

Liver - metabolism

Mice, Inbred C57BL

RNA, Messenger - genetics

Punctures

Receptors, Tumor Necrosis Factor, Type I - genetics

Reverse Transcriptase Polymerase Chain Reaction

Sepsis - mortality

Cecum - pathology

Animals

Interleukin 1 Receptor Antagonist Protein

Mice

Sepsis - microbiology

Details

Title: Subtitle: Anti-inflammatory response is associated with mortality and severity of infection in sepsis
Creators: Alix Ashare - Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa College of Medicine, 200 Hawkins Dr., C-33 GH, Iowa City, IA 52242, USA. alix-ashare@uiowa.edu
Linda S Powers
Noah S Butler
Kevin C Doerschug
Martha M Monick
Gary W Hunninghake
Resource Type: Journal article
Publication Details: American journal of physiology. Lung cellular and molecular physiology, Vol.288(4), pp.L633-640
DOI: 10.1152/ajplung.00231.2004
PMID: 15579629
NLM abbreviation: Am J Physiol Lung Cell Mol Physiol
ISSN: 1040-0605
eISSN: 1522-1504
Publisher: United States
Grant note: HL-60316 / NHLBI NIH HHS ES-09607 / NIEHS NIH HHS
Language: English
Date published: 04/2005
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984001147302771

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