Relationship between antimicrobial proteins and airway inflammation and infection in cystic fibrosis.
Antimicrobial proteins are important in lung defense and are potential therapeutic agents in chronic airways infection such as seen in cystic fibrosis (CF). In preparation for future clinical studies, we sought (1) to determine levels of three antimicrobial proteins [lactoferrin, lysozyme, and secretory leukoprotease inhibitor (SLPI)] in the CF airway and (2) to examine the relationships between these antimicrobial proteins and airway inflammation and infection. We examined bronchoalveolar lavage fluid (BALF) from 45 individuals with CF and 23 disease control individuals. Airway inflammation was measured through BALF neutrophil counts and neutrophil elastase activity. Infection was assessed through quantitative counts of CF-related bacterial pathogens. BALF lysozyme activity and lactoferrin levels were elevated in individuals with CF compared to controls whereas SLPI levels were not different between the groups. Among the CF subjects, lysozyme activity and lactoferrin increased with age while SLPI decreased with age. Lysozyme activity and lactoferrin concentrations correlated positively with neutrophil counts but not with bacterial colony counts. SLPI levels were inversely related to both neutrophil counts and bacterial colony counts. This study provides information concerning the levels of antimicrobial proteins present in the CF airway that are relevant to future clinical trials of these compounds and demonstrates clear relationships between antimicrobial protein-specific levels and airway inflammation and infection.
Sagel
Scott D
SD
Department of Pediatrics, The Children's Hospital and University of Colorado Denver School of Medicine, Aurora, Colorado 80045, USA. sagel.scott@tchden.org
Sontag
Marci K
MK
Accurso
Frank J
FJ
D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000032:analysis; D001991:Bronchitis / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003550:Cystic Fibrosis / Q000150:complications / Q000175:diagnosis / Q000276:immunology*; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D007781:Lactoferrin / Q000032:analysis / Q000276:immunology*; D007958:Leukocyte Count; D019272:Leukocyte Elastase / Q000032:analysis; D008297:Male; D009113:Muramidase / Q000032:analysis / Q000276:immunology*; D012141:Respiratory Tract Infections / Q000150:complications / Q000276:immunology; D053481:Secretory Leukocyte Peptidase Inhibitor / Q000032:analysis / Q000276:immunology*; D055815:Young Adult
D015415:Biomarkers; D053481:Secretory Leukocyte Peptidase Inhibitor; D009113:Muramidase; D007781:Lactoferrin; D019272:Leukocyte Elastase