Transforming growth factor beta-1 and interleukin-17 gene transcription in peripheral blood mononuclear cells and the human response to infection.
BACKGROUND
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.
White
Mary
M
Department of Anaesthesia, St. James Hospital, Dublin 8, Ireland; Institute of Molecular Medicine, Trinity College Dublin, Ireland. drmbwhite@yahoo.co.uk
Lawless
Matthew W
MW
O'Dwyer
Michael J
MJ
Grealy
Robert
R
Connell
Brian O
BO
Stordeur
Patrick
P
Kelleher
Dermot
D
McManus
Ross
R
Ryan
Thomas
T
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000368:Aged; D000369:Aged, 80 and over; D016470:Bacteremia / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D003710:Demography; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D018628:Gene Dosage / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D020381:Interleukin-17 / Q000097:blood* / Q000235:genetics*; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy / Q000235:genetics*; D014158:Transcription, Genetic; D053773:Transforming Growth Factor beta1 / Q000097:blood* / Q000235:genetics*
D000305:Adrenal Cortex Hormones; C508717:IL17A protein, human; D020381:Interleukin-17; D012333:RNA, Messenger; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1