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

Hdl Handle:
http://hdl.handle.net/10147/207837
Title:
Transforming growth factor beta-1 and interleukin-17 gene transcription in peripheral blood mononuclear cells and the human response to infection.
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
Citation:
Cytokine. 2010 Jun;50(3):322-7. Epub 2010 Mar 5.
Journal:
Cytokine
Issue Date:
1-Feb-2012
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
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
ISSN:
1096-0023 (Electronic); 1043-4666 (Linking)

Full metadata record

DC FieldValue Language
dc.contributor.authorWhite, Maryen_GB
dc.contributor.authorLawless, Matthew Wen_GB
dc.contributor.authorO'Dwyer, Michael Jen_GB
dc.contributor.authorGrealy, Roberten_GB
dc.contributor.authorConnell, Brian Oen_GB
dc.contributor.authorStordeur, Patricken_GB
dc.contributor.authorKelleher, Dermoten_GB
dc.contributor.authorMcManus, Rossen_GB
dc.contributor.authorRyan, Thomasen_GB
dc.date.accessioned2012-02-01T10:46:07Z-
dc.date.available2012-02-01T10:46:07Z-
dc.date.issued2012-02-01T10:46:07Z-
dc.identifier.citationCytokine. 2010 Jun;50(3):322-7. Epub 2010 Mar 5.en_GB
dc.identifier.issn1096-0023 (Electronic)en_GB
dc.identifier.issn1043-4666 (Linking)en_GB
dc.identifier.pmid20207161en_GB
dc.identifier.doi10.1016/j.cyto.2010.01.003en_GB
dc.identifier.urihttp://hdl.handle.net/10147/207837-
dc.description.abstractINTRODUCTION: 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.en_GB
dc.language.isoengen_GB
dc.subject.meshAdrenal Cortex Hormones/therapeutic useen_GB
dc.subject.meshAgeden_GB
dc.subject.meshAged, 80 and overen_GB
dc.subject.meshBacteremia/genetics/immunologyen_GB
dc.subject.meshCase-Control Studiesen_GB
dc.subject.meshDemographyen_GB
dc.subject.meshEnzyme-Linked Immunosorbent Assayen_GB
dc.subject.meshFemaleen_GB
dc.subject.meshGene Dosage/geneticsen_GB
dc.subject.meshGene Expression Regulationen_GB
dc.subject.meshHumansen_GB
dc.subject.meshInterleukin-17/*blood/*geneticsen_GB
dc.subject.meshLeukocytes, Mononuclear/*metabolismen_GB
dc.subject.meshMaleen_GB
dc.subject.meshRNA, Messenger/genetics/metabolismen_GB
dc.subject.meshSepsis/drug therapy/*geneticsen_GB
dc.subject.mesh*Transcription, Geneticen_GB
dc.subject.meshTransforming Growth Factor beta1/*blood/*geneticsen_GB
dc.titleTransforming growth factor beta-1 and interleukin-17 gene transcription in peripheral blood mononuclear cells and the human response to infection.en_GB
dc.contributor.departmentDepartment of Anaesthesia, St. James Hospital, Dublin 8, Ireland; Institute of, Molecular Medicine, Trinity College Dublin, Ireland. drmbwhite@yahoo.co.uken_GB
dc.identifier.journalCytokineen_GB
dc.description.provinceLeinster-

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