Mary White1, Ignacio Martin-Loeches2, Matthew W Lawless3, Michael J O'Dwyer4, Derek G Doherty5, Vincent Young6, Dermot Kelleher3, Ross McManus3, Thomas Ryan4. 1. Department of Anaesthesia and Intensive Care Medicine, St James Hospital, Dublin, Ireland; Department of Clinical Medicine, Trinity College Dublin, Dublin, Ireland. Electronic address: drmbwhite@yahoo.co.uk. 2. Department of Anaesthesia and Intensive Care Medicine, St James Hospital, Dublin, Ireland; Critical Care Department, Joan XXIII University Hospital, University Rovira i Virgili, IISPV, CIBER Enfermedades Respiratorias (CIBERes) Tarragona, Spain. 3. Department of Clinical Medicine, Trinity College Dublin, Dublin, Ireland. 4. Department of Anaesthesia and Intensive Care Medicine, St James Hospital, Dublin, Ireland. 5. Department of Immunology, Institute of Molecular Medicine, Trinity College Dublin, Dublin, Ireland. 6. Department of Cardiothoracic Surgery, St James Hospital, Dublin, Ireland.
Abstract
BACKGROUND: Infection in humans has been linked with altered cytokine gene transcription. It is unclear whether this phenomenon is a consequence of an established disease process or precedes the infective process. The primary end point of this study was to determine whether hospital-acquired pneumonia (HAP) was associated with differential gene expression of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and IL-23p19. The secondary end point was to identify whether alteration in gene expression preceded the clinical onset of infection. METHODS: Sixty consecutive patients undergoing elective thoracic surgery were recruited. HAP was diagnosed as per National Nosocomial Infection Surveillance guidelines. Messenger RNA (mRNA) and protein levels were analyzed preoperatively and 24 h and 5 days postoperatively. RESULTS: Forty-one patients had an uncomplicated recovery. Nineteen patients developed HAP. IL-6, IL-10, IL-12p35, IL-23p19, IL-27p28, TNF-α, and IFN-γ mRNA and protein levels of IL-6, IL-23, and IFN-γ in peripheral blood leukocytes were analyzed before surgery and 24 h and 5 days postsurgery. IL-23p19 mRNA levels were reduced in the pneumonia group (median, 4.19; 10th-90th centile range, 3.90-4.71) compared with the nonpneumonia group (4.50; 3.85-5.32) day 1 postsurgery (P=02). IFN-γ mRNA levels were reduced in the pneumonia group (2.48; 1.20-3.20) compared with nonpneumonia group (2.81; 2.10-3.26) (P=03) day 5 postsurgery. Results are expressed as log to base 10 copy numbers of cytokine mRNA per 10 million β-actin mRNA copy numbers. All values are given as median and 10th to 90th centile range. CONCLUSIONS: Cytokine gene expression is altered immediately following surgery in patients with postoperative HAP.
BACKGROUND:Infection in humans has been linked with altered cytokine gene transcription. It is unclear whether this phenomenon is a consequence of an established disease process or precedes the infective process. The primary end point of this study was to determine whether hospital-acquired pneumonia (HAP) was associated with differential gene expression of interferon (IFN)-γ, tumor necrosis factor (TNF)-α, and IL-23p19. The secondary end point was to identify whether alteration in gene expression preceded the clinical onset of infection. METHODS: Sixty consecutive patients undergoing elective thoracic surgery were recruited. HAP was diagnosed as per National Nosocomial Infection Surveillance guidelines. Messenger RNA (mRNA) and protein levels were analyzed preoperatively and 24 h and 5 days postoperatively. RESULTS: Forty-one patients had an uncomplicated recovery. Nineteen patients developed HAP. IL-6, IL-10, IL-12p35, IL-23p19, IL-27p28, TNF-α, and IFN-γ mRNA and protein levels of IL-6, IL-23, and IFN-γ in peripheral blood leukocytes were analyzed before surgery and 24 h and 5 days postsurgery. IL-23p19 mRNA levels were reduced in the pneumonia group (median, 4.19; 10th-90th centile range, 3.90-4.71) compared with the nonpneumonia group (4.50; 3.85-5.32) day 1 postsurgery (P=02). IFN-γ mRNA levels were reduced in the pneumonia group (2.48; 1.20-3.20) compared with nonpneumonia group (2.81; 2.10-3.26) (P=03) day 5 postsurgery. Results are expressed as log to base 10 copy numbers of cytokine mRNA per 10 million β-actin mRNA copy numbers. All values are given as median and 10th to 90th centile range. CONCLUSIONS: Cytokine gene expression is altered immediately following surgery in patients with postoperative HAP.
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