• Rev Alerg Mex · Nov 2004

    Toll-like receptors: dysregulation in vivo in patients with acute respiratory distress syndrome.

    • Nora E Ramírez Cruz, Carmen Maldonado Bernal, María Luisa Cuevas Urióstegui, Jorge Castañoń, Constantino López Macías, and Armando Isibasi.
    • Unidad de Investigación Médica en Inmunoquímica, Centro Médico Nacional Siglo XXI, IMSS, Mexico City.
    • Rev Alerg Mex. 2004 Nov 1;51(6):210-7.

    ObjectiveTo 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 MethodsIn 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.ResultsDysregulation 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).ConclusionsThus, TLRs gene dysregulation and cytokine profiles are probably important prognostic factors for patient outcome and survival after ARDS.

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