Objective: To determine the time course of the expression of five toll-like receptors (TLRs 1-5) in mixed blood mononuclear cells and their relationship to pro-inflammatory and anti-inflammatory cytokines during acute respiratory distress syndrome (ARDS).
Material and methods: In a prospective, a longitudinal study was done at an intensive-care unit of a university-affiliated hospital. Seven consecutive patients with ARDS were studied. We followed the onset and progression of ARDS, and subsequent patient recovery or death, and compared patient data with data from a group of healthy volunteers. We separated mixed blood mononuclear cells using Ficoll-Hypaque to detect the transcripts of human TLRs 1-5. TLR mRNAs were isolated by semiquantitative reverse-transcription PCR (RT-PCR). Each signal was expressed as the ratio of TLR mRNA to beta-actin. Cytokines, including tumor necrosis factor alpha, interferon gamma, and interleukins 4, 6, 8, 10, and 12, were assayed using commercial ELISA kits.
Results: Dysregulation in the transcription of TLRs gene, principally in ARDS surviving patients, was observed. Down-regulated expressions of TLR1, TLR4, and TLR5 mRNAs were observed in the first 24 h in patients who survived, and probably played a key role in the survival of patients with ARDS caused by sepsis. Serum levels of cytokines such as IL-6, 8 and 10 were significantly increased in patients with ARDS as compared with levels in the healthy volunteers. However, serum levels of IL-12 were lower in patients with ARDS than in the healthy volunteers. There was difference in serum cytokines concentration between survivors and non-survivors patients with ARDS (except for interleukin-10).
Conclusions: Thus, TLRs gene dysregulation and cytokine profiles are probably important prognostic factors for patient outcome and survival after ARDS.