PMID- 20207161 OWN - NLM STAT- MEDLINE DCOM- 20100730 LR - 20100507 IS - 1096-0023 (Electronic) IS - 1043-4666 (Linking) VI - 50 IP - 3 DP - 2010 Jun TI - Transforming growth factor beta-1 and interleukin-17 gene transcription in peripheral blood mononuclear cells and the human response to infection. PG - 322-7 LID - 10.1016/j.cyto.2010.01.003 [doi] AB - 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. CI - Copyright 2010 Elsevier Ltd. All rights reserved. FAU - White, Mary AU - White M AD - Department of Anaesthesia, St. James Hospital, Dublin 8, Ireland; Institute of Molecular Medicine, Trinity College Dublin, Ireland. drmbwhite@yahoo.co.uk FAU - Lawless, Matthew W AU - Lawless MW FAU - O'Dwyer, Michael J AU - O'Dwyer MJ FAU - Grealy, Robert AU - Grealy R FAU - Connell, Brian O AU - Connell BO FAU - Stordeur, Patrick AU - Stordeur P FAU - Kelleher, Dermot AU - Kelleher D FAU - McManus, Ross AU - McManus R FAU - Ryan, Thomas AU - Ryan T LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20100305 PL - England TA - Cytokine JT - Cytokine JID - 9005353 RN - 0 (Adrenal Cortex Hormones) RN - 0 (IL17A protein, human) RN - 0 (Interleukin-17) RN - 0 (RNA, Messenger) RN - 0 (TGFB1 protein, human) RN - 0 (Transforming Growth Factor beta1) SB - IM MH - Adrenal Cortex Hormones/therapeutic use MH - Aged MH - Aged, 80 and over MH - Bacteremia/genetics/immunology MH - Case-Control Studies MH - Demography MH - Enzyme-Linked Immunosorbent Assay MH - Female MH - Gene Dosage/genetics MH - Gene Expression Regulation MH - Humans MH - Interleukin-17/*blood/*genetics MH - Leukocytes, Mononuclear/*metabolism MH - Male MH - RNA, Messenger/genetics/metabolism MH - Sepsis/drug therapy/*genetics MH - *Transcription, Genetic MH - Transforming Growth Factor beta1/*blood/*genetics EDAT- 2010/03/09 06:00 MHDA- 2010/07/31 06:00 CRDT- 2010/03/09 06:00 PHST- 2009/07/22 00:00 [received] PHST- 2009/12/16 00:00 [revised] PHST- 2010/01/10 00:00 [accepted] PHST- 2010/03/09 06:00 [entrez] PHST- 2010/03/09 06:00 [pubmed] PHST- 2010/07/31 06:00 [medline] AID - S1043-4666(10)00006-2 [pii] AID - 10.1016/j.cyto.2010.01.003 [doi] PST - ppublish SO - Cytokine. 2010 Jun;50(3):322-7. doi: 10.1016/j.cyto.2010.01.003. Epub 2010 Mar 5.