title: Severe pneumonia mortality in elderly patients is associated with downregulation of Toll-like receptors 2 and 4 on monocytes.
abstract: BACKGROUND
  Elderly patients with pneumonia have a high mortality rate. Since Toll-like receptor (TLR) signaling is involved in the inflammatory response, we conducted a prospective observational case-control study to assess the relationships of TLR2 and TLR4 mortality with elderly patients with pneumonia.
  
  
  METHODS
  Clinical and laboratory data were collected from these elderly patients with pneumonia (patient group; n = 40) and healthy age-matched subjects (control 1; n = 20). TLR2 and TLR4 expression levels on blood monocytes were examined, and inflammatory cytokine tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1) and interleukin-6 (IL-6) plasma concentrations were analyzed.
  
  
  RESULTS
  Increased TLR2 and TLR4 expression levels were detected in elderly patients with severe pneumonia compared with healthy subjects. Furthermore, we observed a positive correlation between TLR2 and TLR4 expression levels and IL-1 and IL-6 levels, and TLR2- and TLR4-positive cell percent expressions correlated with TNF-α levels. By day 28 of observation, the mortality rate of the patient group was 30%. Decreased TLR2 and TLR4 expression was observed in deceased patients compared with survivors. APACHE (Acute Physiology and Chronic Health Evaluation) II scores and CURB-65 scores (Confusion, blood Urea nitrogen, Respiratory rate and low Blood pressure scores) were lower in survivors.
  
  
  CONCLUSIONS
  These findings demonstrate a previously undocumented association between mortality in elderly patients with severe pneumonia and decreased TLR2 and TLR4 expression. Our results highlight that TLRs can be targeted in the development of improved immune modulation therapies for these patients.
authors: Department of Central Intensive Care Unit (LT, QL, JB, SM), Geriatric Department (HZ), and The Central Laboratory Department (YL), East Hospital, TongJi University, Shanghai, China.
authors: Lunxian
authors: L
authors: Tang
authors: Qinchuan
authors: Q
authors: Li
authors: Jianwen
authors: J
authors: Bai
authors: Hua
authors: H
authors: Zhang
authors: Ying
authors: Y
authors: Lu
authors: Shaolin
authors: S
authors: Ma
mesh_terms: D018806:APACHE; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000378:metabolism; D016022:Case-Control Studies; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007375:Interleukin-1 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009000:Monocytes / Q000378:metabolism*; D011014:Pneumonia / Q000378:metabolism* / Q000401:mortality*; D011446:Prospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate; D051195:Toll-Like Receptor 2 / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D015415:Biomarkers; D007375:Interleukin-1; D015850:Interleukin-6; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha