title: IL-13 blockade reduces lung inflammation after Ascaris suum challenge in cynomolgus monkeys.
abstract: BACKGROUND
  Airway inflammation is a hallmark feature of asthma and a driver of airway hyperresponsiveness. IL-13 is a key inducer of airway inflammation in rodent models of respiratory disease, but a role for IL-13 has not been demonstrated in primates.
  
  
  OBJECTIVE
  We sought to test the efficacy of a neutralizing antibody to human IL-13 in a cynomolgus monkey model of lung inflammation.
  
  
  METHODS
  Using cynomolgus monkeys (Macaca fascicularis) that are sensitized to Ascaris suum through natural exposure, we developed a reproducible model of acute airway inflammation after segmental A suum antigen challenge. This model was used to test the in vivo efficacy of mAb13.2, a mouse mAb directed against human IL-13, and IMA-638, the humanized counterpart of mAb13.2. Bronchoalveolar lavage (BAL) cells and BAL fluid were collected before and after antigen challenge and assayed for cellular content by means of differential count.
  
  
  RESULTS
  Total BAL cell count, eosinophil number, and neutrophil number were all reduced in animals treated with mAb13.2 or IMA-638 compared with values in control animals that were untreated, given saline, or treated with human IgG of irrelevant specificity. In addition, levels of eotaxin and RANTES in BAL fluid were reduced in anti-IL-13-treated animals compared with levels seen in control animals.
  
  
  CONCLUSIONS
  These findings support a role for IL-13 in maintaining lung inflammation in response to allergen challenge in nonhuman primates.
  
  
  CONCLUSIONS
  IL-13 neutralization with a specific antibody could be a useful therapeutic strategy for asthma.
authors: Wyeth Research, Cambridge, MA 02140, USA.
authors: Andrea
authors: A
authors: Bree
authors: Franklin J
authors: FJ
authors: Schlerman
authors: Michael
authors: M
authors: Wadanoli
authors: Lioudmila
authors: L
authors: Tchistiakova
authors: Kimberly
authors: K
authors: Marquette
authors: Xiang-Yang
authors: XY
authors: Tan
authors: Bruce A
authors: BA
authors: Jacobson
authors: Angela
authors: A
authors: Widom
authors: Timothy A
authors: TA
authors: Cook
authors: Nancy
authors: N
authors: Wood
authors: Suresh
authors: S
authors: Vunnum
authors: Rustem
authors: R
authors: Krykbaev
authors: Xin
authors: X
authors: Xu
authors: Debra D
authors: DD
authors: Donaldson
authors: Samuel J
authors: SJ
authors: Goldman
authors: Joseph
authors: J
authors: Sypek
authors: Marion T
authors: MT
authors: Kasaian
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019138:Antibodies, Blocking / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000947:Antigens, Helminth / Q000276:immunology; D001196:Ascariasis / Q000276:immunology*; D017165:Ascaris suum; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D016207:Cytokines / Q000096:biosynthesis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D018793:Interleukin-13 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology; D008252:Macaca fascicularis; D008297:Male; D008969:Molecular Sequence Data; D011014:Pneumonia / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control*; D017386:Sequence Homology, Amino Acid
chemical_list: D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth; D016207:Cytokines; D018793:Interleukin-13