title: Microarray analysis identifies IL-1 receptor type 2 as a novel candidate biomarker in patients with acute respiratory distress syndrome.
abstract: BACKGROUND
  Acute respiratory distress syndrome (ARDS) is a disease associated with a high mortality rate. The initial phase is characterized by induction of inflammatory cytokines and chemokines and influx of circulating inflammatory cells, including macrophages which play a pivotal role in the innate and adaptive immune responses to injury. Growing evidence points to phenotypic heterogeneity and plasticity between various macrophage activation states.
  
  
  METHODS
  In this study, gene expression in alveolar macrophages and circulating leukocytes from healthy control subjects and patients with ARDS was assessed by mRNA microarray analysis.
  
  
  RESULTS
  Both alveolar macrophages and circulating leukocytes demonstrated up-regulation of genes encoding chemotactic factors, antimicrobial peptides, chemokine receptors, and matrix metalloproteinases. Two genes, the pro-inflammatory S100A12 and the anti-inflammatory IL-1 decoy receptor IL-1R2 were significantly induced in both cell populations in ARDS patients, which was confirmed by protein quantification. Although S100A12 levels did not correlate with disease severity, there was a significant association between early plasma levels of IL-1R2 and APACHE III scores at presentation. Moreover, higher levels of IL-1R2 in plasma were observed in non-survivors as compared to survivors at later stages of ARDS.
  
  
  CONCLUSIONS
  These results suggest a hybrid state of alveolar macrophage activation in ARDS, with features of both alternative activation and immune tolerance/deactivation.. Furthermore, we have identified a novel plasma biomarker candidate in ARDS that correlates with the severity of systemic illness and mortality.
authors: Melissa A
authors: MA
authors: Kovach
authors: Kathleen A
authors: KA
authors: Stringer
authors: Rachel
authors: R
authors: Bunting
authors: Xiaoying
authors: X
authors: Wu
authors: Lani
authors: L
authors: San Mateo
authors: Michael W
authors: MW
authors: Newstead
authors: Robert
authors: R
authors: Paine
authors: Theodore J
authors: TJ
authors: Standiford
mesh_terms: D018806:APACHE; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D005819:Genetic Markers; D006801:Humans; D007962:Leukocytes / Q000276:immunology / Q000378:metabolism; D008262:Macrophage Activation; D016676:Macrophages, Alveolar / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010865:Pilot Projects; D011237:Predictive Value of Tests; D011379:Prognosis; D016032:Randomized Controlled Trials as Topic; D053574:Receptors, Interleukin-1 Type II / Q000097:blood / Q000235:genetics* / Q000276:immunology; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000175:diagnosis / Q000235:genetics* / Q000276:immunology; D000067616:S100A12 Protein / Q000235:genetics; D012720:Severity of Illness Index
chemical_list: D005819:Genetic Markers; C508592:IL1R2 protein, human; D053574:Receptors, Interleukin-1 Type II; D000067616:S100A12 Protein; C090441:S100A12 protein, human