Loading...
Transforming growth factor beta-1 and interleukin-17 gene transcription in peripheral blood mononuclear cells and the human response to infection.
White, Mary Lawless, Matthew W O'Dwyer, Michael J Grealy, Robert Connell, Brian O Stordeur, Patrick Kelleher, Dermot McManus, Ross Ryan, Thomas
White, Mary
Lawless, Matthew W
O'Dwyer, Michael J
Grealy, Robert
Connell, Brian O
Stordeur, Patrick
Kelleher, Dermot
McManus, Ross
Ryan, Thomas
Advisors
Editors
Other Contributors
Date
2012-02-01T10:46:07Z
Date Submitted
Keywords
Other Subjects
Subject 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
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
Planned Date
Start Date
Collaborators
Principal Investigators
Alternative Titles
Publisher
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)
1043-4666 (Linking)
eISSN
ISBN
DOI
10.1016/j.cyto.2010.01.003
PMID
20207161