IP-10 is a potential biomarker of cystic fibrosis acute pulmonary exacerbations.

Academic Article

Abstract

  • BACKGROUND: Cystic fibrosis (CF) is characterized by acute pulmonary exacerbations (APE). The CF nasal airway exhibits a similar ion transport defect as the lung, and colonization, infection, and inflammation within the nasal passages are common among CF patients. Nasal lavage fluid (NLF) is a minimally invasive means to collect upper airway samples. METHODS: We collected NLF at the onset and resolution of CF APE and compared a 27-plex cytokine profile to stable CF outpatients and normal controls. We also tested IP-10 levels in the bronchoalveolar lavage fluid (BALF) of CF patients. Well-differentiated murine sinonasal monolayers were exposed to bacterial stimulus, and IP-10 levels were measured to test epithelial secretion. RESULTS: Subjects hospitalized for APE had elevated IP-10 (2582 pg/mL [95% CL of mean: 818,8165], N=13) which significantly decreased (647 pg/mL [357,1174], P<0.05, N =13) following antimicrobial therapy. Stable CF outpatients exhibited intermediately elevated levels (680 pg/mL [281,1644], N=13) that were less than CF inpatients upon admission (P=0.056) but not significantly different than normal controls (342 pg/mL [110,1061]; P=0.3, N=10). IP-10 was significantly increased in CF BALF (2673 pg/mL [1306,5458], N=10) compared to healthy post-lung transplant patients (8.4 pg/mL [0.03,2172], N=5, P<0.001). IP-10 levels from well-differentiated CF murine nasal epithelial monolayers exposed to Pseudomonas PAO-1 bacteria-free prep or LPS (100 nM) apically for 24 hours were significantly elevated (1159 ± 147, P<0.001 for PAO-1; 1373 ± 191, P<0.001 for LPS vs. 305 ± 68 for vehicle controls). Human sino-nasal epithelial cells derived from CF patients had a similar response to LPS (34% increase, P<0.05, N=6). CONCLUSIONS: IP-10 is elevated in the nasal lavage of CF patients with APE and responds to antimicrobial therapy. IP-10 is induced by airway epithelia following stimulation with bacterial pathogens in a murine model. Additional research regarding IP-10 as a potential biomarker is warranted.
  • Published In

  • PLoS ONE  Journal
  • Keywords

  • Acute Disease, Adolescent, Adult, Animals, Biomarkers, Bronchoalveolar Lavage Fluid, Case-Control Studies, Cell Compartmentation, Cell Differentiation, Cells, Cultured, Chemokine CXCL10, Cystic Fibrosis, Cytokines, Disease Models, Animal, Disease Progression, Epithelial Cells, Female, Humans, Inflammation, Inpatients, Male, Middle Aged, Nasal Lavage Fluid, Serous Membrane, Young Adult
  • Digital Object Identifier (doi)

    Authorlist

  • Solomon GM; Frederick C; Zhang S; Gaggar A; Harris T; Woodworth BA; Steele C; Rowe SM
  • Start Page

  • e72398
  • Volume

  • 8
  • Issue

  • 8