title: IP-10 is a potential biomarker of cystic fibrosis acute pulmonary exacerbations.
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.
authors: Department of Medicine, Division of Pulmonary Sciences and Critical Care Medicine, University of Colorado Denver, Denver, Colorado, United States of America.
authors: George M
authors: GM
authors: Solomon
authors: Carla
authors: C
authors: Frederick
authors: Shaoyan
authors: S
authors: Zhang
authors: Amit
authors: A
authors: Gaggar
authors: Tom
authors: T
authors: Harris
authors: Bradford A
authors: BA
authors: Woodworth
authors: Chad
authors: C
authors: Steele
authors: Steven M
authors: SM
authors: Rowe
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid; D016022:Case-Control Studies; D002451:Cell Compartmentation; D002454:Cell Differentiation; D002478:Cells, Cultured; D054357:Chemokine CXCL10 / Q000378:metabolism*; D003550:Cystic Fibrosis / Q000378:metabolism* / Q000473:pathology*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D006801:Humans; D007249:Inflammation / Q000473:pathology; D007297:Inpatients; D008297:Male; D008875:Middle Aged; D017817:Nasal Lavage Fluid; D012704:Serous Membrane / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D015415:Biomarkers; C114753:CXCL10 protein, human; D054357:Chemokine CXCL10; C485433:Cxcl10 protein, mouse; D016207:Cytokines
references: Respirology. 2005 Mar;10(2):177-82
references: 15823182
references: J Cyst Fibros. 2009 Sep;8(5):338-47
references: 19604728
references: N Engl J Med. 2010 Dec 2;363(23):2233-47
references: 21121836
references: J Allergy Clin Immunol. 2003 Jun;111(6):1171-83; quiz 1184
references: 12789212
references: Am J Physiol Cell Physiol. 2006 Jul;291(1):C34-9
references: 16467404
references: Cytokine. 2010 May;50(2):152-7
references: 20181491
references: Arch Otolaryngol Head Neck Surg. 1996 Nov;122(11):1209-13
references: 8906056
references: Eur Respir J. 2005 Aug;26(2):319-38
references: 16055882
references: Thorax. 2003 Jan;58(1):63-7
references: 12511724
references: J Lab Clin Med. 2002 Mar;139(3):173-80
references: 11944028
references: J Allergy Clin Immunol. 1992 Sep;90(3 Pt 2):547-52
references: 1527348
references: J Cyst Fibros. 2012 Mar;11(2):100-7
references: 22035905
references: J Cyst Fibros. 2013 May;12(3):249-57
references: 22990051
references: FASEB J. 2004 Feb;18(2):329-31
references: 14657006
references: Am J Rhinol Allergy. 2012 Jan-Feb;26(1):70-5
references: 22391086
references: Am J Respir Crit Care Med. 2012 Nov 1;186(9):857-65
references: 22904182
references: J Pediatr. 2002 Dec;141(6):811-7
references: 12461498
references: J Cyst Fibros. 2006 Aug;5(3):145-51
references: 16503423
references: Nat Genet. 1992 Nov;2(3):240-8
references: 1285365
references: Antimicrob Agents Chemother. 2009 Apr;53(4):1546-51
references: 19139287
references: Lancet. 1990 May 5;335(8697):1077-8
references: 1970379
references: Am J Pathol. 2004 May;164(5):1557-66
references: 15111302
references: Am J Rhinol. 2007 Sep-Oct;21(5):533-7
references: 17999784
references: J Immunol. 2001 Nov 15;167(10):5887-94
references: 11698465
references: Chest. 2013 Jul;144(1):200-207
references: 23412700
references: N Engl J Med. 2005 May 12;352(19):1992-2001
references: 15888700
references: J Leukoc Biol. 2000 Jul;68(1):1-8
references: 10914483
references: Am J Respir Crit Care Med. 2007 Apr 15;175(8):822-8
references: 17234902
references: Proc Am Thorac Soc. 2007 Aug 1;4(4):406-17
references: 17652508
references: Biotechniques. 2007 Aug;43(2):195-6, 198, 200 passim
references: 17824387
references: Am J Rhinol Allergy. 2009 Mar-Apr;23(2):149-52
references: 19401039
references: Eur Respir J. 2003 Apr;21(4):600-5
references: 12762342
references: Int J Tuberc Lung Dis. 2009 Jun;13(6):731-6
references: 19460249
references: Am J Physiol Lung Cell Mol Physiol. 2006 May;290(5):L909-18
references: 16339779
references: Science. 1992 May 8;256(5058):774-9
references: 1375392
references: PLoS One. 2012;7(8):e42748
references: 22916155
references: Laryngoscope. 1995 Apr;105(4 Pt 1):354-8
references: 7715376