IL-13 blockade reduces lung inflammation after Ascaris suum challenge in cynomolgus monkeys.
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.
Bree
Andrea
A
Wyeth Research, Cambridge, MA 02140, USA.
Schlerman
Franklin J
FJ
Wadanoli
Michael
M
Tchistiakova
Lioudmila
L
Marquette
Kimberly
K
Tan
Xiang-Yang
XY
Jacobson
Bruce A
BA
Widom
Angela
A
Cook
Timothy A
TA
Wood
Nancy
N
Vunnum
Suresh
S
Krykbaev
Rustem
R
Xu
Xin
X
Donaldson
Debra D
DD
Goldman
Samuel J
SJ
Sypek
Joseph
J
Kasaian
Marion T
MT
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
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D000947:Antigens, Helminth; D016207:Cytokines; D018793:Interleukin-13