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


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.
Ramírez Cruz
Nora E
NE
Unidad de Investigación Médica en Inmunoquímica, Centro Médico Nacional Siglo XXI, IMSS, Mexico City.
Maldonado Bernal
Carmen
C
Cuevas Urióstegui
María Luisa
ML
Castañoń
Jorge
J
López Macías
Constantino
C
Isibasi
Armando
A
D000368:Aged; D015415:Biomarkers; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D007378:Interleukins / Q000097:blood; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012333:RNA, Messenger / Q000096:biosynthesis / Q000097:blood; D011956:Receptors, Cell Surface / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D012128:Respiratory Distress Syndrome / Q000097:blood* / Q000209:etiology / Q000401:mortality; D016019:Survival Analysis; D018746:Systemic Inflammatory Response Syndrome / Q000150:complications; D051194:Toll-Like Receptor 1; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015415:Biomarkers; D007378:Interleukins; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; C495346:TLR5 protein, human; D051194:Toll-Like Receptor 1; D051197:Toll-Like Receptor 4; D051198:Toll-Like Receptor 5; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma