title: Lack of effect of bovine lactoferrin in respiratory syncytial virus replication and clinical disease severity in the mouse model.
abstract: BACKGROUND
  Lactoferrin (LF) is a glycoprotein present in human milk with known antimicrobial effects. In vitro, LF has demonstrated antiviral activity against respiratory syncytial virus (RSV). We sought to assess the effect of bovine (b)LF in RSV replication, lung inflammation and function, cytokine profiles and clinical disease in an in vivo murine model.
  
  
  METHODS
  Female BALB/c mice were inoculated with 10(7)PFU RSV A2 or 10% EMEM. bLF or placebo (DPBS) were administered once or twice daily by oral gavage or intraperitoneal (IP) injection at doses ranging from 2 to 10mg/animal/day, from 48h before until 96h post-RSV inoculation. Bronchoalveolar lavage (BAL), whole lung and serum samples were harvested on day 5 post-inoculation to asses RSV loads, lung inflammation and cytokine concentrations. Weight loss, airway obstruction and disease severity were assessed daily in all groups.
  
  
  RESULTS
  On day 5 post-inoculation BAL RSV loads, lung inflammation and serum innate, Th1, Th2 and Th17 cytokine concentrations showed no differences between RSV infected mice treated with bLF and RSV infected but untreated mice independent of bLF dosing and administration route (p>0.05). In addition, all bLF groups showed similar weight loss, degree of airway obstruction, and disease severity scores on days 1-5 post-inoculation which was comparable to infected untreated mice (p>0.05) but higher than uninfected controls.
  
  
  CONCLUSIONS
  Administration of oral or IP bLF at different doses did not demonstrate antiviral activity or significant effects on disease severity in the RSV mouse model. Whether these observations could be extrapolated to infants at risk for RSV infection needs to be further explored.
authors.affiliation: Center for Vaccines and Immunity, The Research Institute at Nationwide Children's Hospital, The Ohio State University, Columbus, OH, United States.
authors.forename: Lucien
authors.initials: L
authors.lastname: Gualdi
authors.forename: Sara
authors.initials: S
authors.lastname: Mertz
authors.forename: Ana M
authors.initials: AM
authors.lastname: Gomez
authors.forename: Octavio
authors.initials: O
authors.lastname: Ramilo
authors.forename: Anja
authors.initials: A
authors.lastname: Wittke
authors.forename: Asuncion
authors.initials: A
authors.lastname: Mejias
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000821:virology; D016207:Cytokines / Q000097:blood / Q000187:drug effects; D004195:Disease Models, Animal; D005260:Female; D007781:Lactoferrin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D008168:Lung / Q000503:physiopathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D011014:Pneumonia / Q000188:drug therapy / Q000821:virology; D012129:Respiratory Function Tests; D018357:Respiratory Syncytial Virus Infections / Q000188:drug therapy* / Q000821:virology; D012136:Respiratory Syncytial Viruses / Q000187:drug effects*; D019562:Viral Load / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000890:Anti-Infective Agents; D000998:Antiviral Agents; D016207:Cytokines; D007781:Lactoferrin
keywords: Bovine lactoferrin; Breast feeding; Disease severity; RSV