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    Transforming growth factor beta-1 and interleukin-17 gene transcription in peripheral blood mononuclear cells and the human response to infection.

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    Authors
    White, Mary
    Lawless, Matthew W
    O'Dwyer, Michael J
    Grealy, Robert
    Connell, Brian O
    Stordeur, Patrick
    Kelleher, Dermot
    McManus, Ross
    Ryan, Thomas
    Affiliation
    Department of Anaesthesia, St. James Hospital, Dublin 8, Ireland; Institute of, Molecular Medicine, Trinity College Dublin, Ireland. drmbwhite@yahoo.co.uk
    Issue Date
    2012-02-01T10:46:07Z
    MeSH
    Adrenal Cortex Hormones/therapeutic use
    Aged
    Aged, 80 and over
    Bacteremia/genetics/immunology
    Case-Control Studies
    Demography
    Enzyme-Linked Immunosorbent Assay
    Female
    Gene Dosage/genetics
    Gene Expression Regulation
    Humans
    Interleukin-17/*blood/*genetics
    Leukocytes, Mononuclear/*metabolism
    Male
    RNA, Messenger/genetics/metabolism
    Sepsis/drug therapy/*genetics
    *Transcription, Genetic
    Transforming Growth Factor beta1/*blood/*genetics
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    Citation
    Cytokine. 2010 Jun;50(3):322-7. Epub 2010 Mar 5.
    Journal
    Cytokine
    URI
    http://hdl.handle.net/10147/207837
    DOI
    10.1016/j.cyto.2010.01.003
    PubMed ID
    20207161
    Abstract
    INTRODUCTION: The occurrence of severe sepsis may be associated with deficient pro-inflammatory cytokine production. Transforming growth factor beta-1 (TGFbeta-1) predominantly inhibits inflammation and may simultaneously promote IL-17 production. Interleukin-17 (IL-17) is a recently described pro-inflammatory cytokine, which may be important in auto-immunity and infection. We investigated the hypothesis that the onset of sepsis is related to differential TGFbeta-1 and IL-17 gene expression. METHODS: A prospective observational study in a mixed intensive care unit (ICU) and hospital wards in a university hospital. Patients (59) with severe sepsis; 15 patients with gram-negative bacteraemia but without critical illness and 10 healthy controls were assayed for TGFbeta-1, IL-17a, IL-17f, IL-6 and IL-1beta mRNA in peripheral blood mononuclear cells (PBMC) by quantitative real-time PCR and serum protein levels by ELISA. RESULTS: TGFbeta-1 mRNA levels are reduced in patients with bacteraemia and sepsis compared with controls (p=0.02). IL-6 mRNA levels were reduced in bacteraemic patients compared with septic patients and controls (p=0.008). IL-1beta mRNA levels were similar in all groups, IL-17a and IL-17f mRNA levels are not detectable in peripheral blood mononuclear cells. IL-6 protein levels were greater in patients with sepsis than bacteraemic and control patients (p<0.0001). Activated TGFbeta-1 and IL-17 protein levels were similar in all groups. IL-1beta protein was not detectable in the majority of patients. CONCLUSIONS: Down regulation of TGFbeta-1 gene transcription was related to the occurrence of infection but not the onset of sepsis. Interleukin-17 production in PBMC may not be significant in the human host response to infection.
    Language
    eng
    ISSN
    1096-0023 (Electronic)
    1043-4666 (Linking)
    ae974a485f413a2113503eed53cd6c53
    10.1016/j.cyto.2010.01.003
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