Severe pneumonia mortality in pediatric patients is associated with downregulation of Toll-like receptors 2 and 4 on monocytes

Abstract

BACKGROUND: Pediatric 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 in patients with pneumonia.

METHODS: Clinical and laboratory data were collected from these pediatric patients with pneumonia (patient group;n=23) and healthy age-matched subjects (control 1; n=15). 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 pediatric 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 36%. 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 pediatric 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 children.