RGD Reference Report - Thymic stromal lymphopoietin mediates the host response and increases mortality during sepsis. - Rat Genome Database

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Thymic stromal lymphopoietin mediates the host response and increases mortality during sepsis.

Authors: Kuethe, Joshua W  Prakash, Priya S  Midura, Emily F  Johnson, Bobby L  Kasten, Kevin R  Caldwell, Charles C 
Citation: Kuethe JW, etal., J Surg Res. 2014 Sep;191(1):19-24. doi: 10.1016/j.jss.2014.05.024. Epub 2014 May 20.
RGD ID: 38549375
Pubmed: PMID:24990542   (View Abstract at PubMed)
DOI: DOI:10.1016/j.jss.2014.05.024   (Journal Full-text)


BACKGROUND: Sepsis and subsequent multiorgan system failure is associated with high rates of mortality and morbidity. Thymic stromal lymphopoietin (TSLP) is a cytokine that can be produced by keratinocytes and epithelial cells. Primarily, TSLP has been shown to promote counter-inflammatory processes. However, its potential expression or role in the pathogenesis of sepsis is largely unexplored. We hypothesized that TSLP is expressed during sepsis and TSLP blockade would alter the immune response and mortality.
MATERIALS AND METHODS: Mice underwent cecal ligation and puncture (CLP) to produce a physiologically relevant murine model for sepsis. Cohorts were either treated with neutralizing TSLP antibodies or isotype controls before the CLP to determine changes in survival, bacterial loads, cytokine levels, and neutrophil function.
RESULTS: It was observed that TSLP levels peaked at 6 h and remained detectable up to 48 h after CLP. Mice pretreated with neutralizing TSLP showed decreased mortality and bacterial load after CLP. Additionally, we determined that septic mice pretreated with the anti-TSLP antibody had increased tumor necrosis factor alpha and oxidative burst as well as increased interleukin 17 and neutrophil numbers compared with mice pretreated with isotype controls.
CONCLUSIONS: TSLP levels peak early but are sustained during the first 48 h of sepsis. We speculate that TSLP blunts the neutrophil response resulting in increased bacterial load and mortality.



RGD Manual Disease Annotations    Click to see Annotation Detail View
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
TSLPHumanSepsis treatmentISOTslp (Mus musculus) RGD 
TslpRatSepsis treatmentISOTslp (Mus musculus) RGD 
TslpMouseSepsis treatmentIMP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Tslp  (thymic stromal lymphopoietin)

Genes (Mus musculus)
Tslp  (thymic stromal lymphopoietin)

Genes (Homo sapiens)
TSLP  (thymic stromal lymphopoietin)


Additional Information