PMID- 19037805
OWN - NLM
STAT- MEDLINE
DCOM- 20090130
LR  - 20081127
IS  - 1092-874X (Electronic)
IS  - 1091-5818 (Linking)
VI  - 27
IP  - 5
DP  - 2008 Sep-Oct
TI  - Preclinical safety and pharmacology of an anti-human interleukin-13 monoclonal 
      antibody in normal macaques and in macaques with allergic asthma.
PG  - 351-8
LID - 10.1080/10915810802430509 [doi]
AB  - Interleukin-13 (IL-13) plays a central role in chronic airway diseases, including 
      asthma. These studies were conducted to evaluate the safety of administration of 
      a human anti-IL-13 monoclonal antibody (mAb) to normal macaques and in macaques 
      with allergic asthma. In addition, serum and bronchioalveolar lavage fluid were 
      collected from allergic cynomolgus macaques in order to identify potential 
      surrogate markers of IL-13 pharmacology that could be useful for subsequent 
      clinical trials. In vitro studies demonstrated that the anti-IL-13 mAb inhibited 
      the pharmacological actions of both human and cynomolgus macaque IL-13. Allergic 
      macaques were treated systemically with 10 mg/kg anti-IL-13 mAb 1 day prior to 
      inhaled Ascaris suum antigen challenge. Normal macaques were dosed intravenously 
      with anti-IL-13 once per week for 3 weeks at doses of 10 or 50 mg/kg. Treatment 
      of macaques with the anti-IL-13 mAb was not associated with any toxicologically 
      significant findings. A slight treatment-related but nonadverse decrease in 
      platelet counts was observed in both the normal and allergic macaques. In 
      allergic macaques, the anti-IL-13 mAb treatment did not affect lung function, 
      lung eosinophilia, or serum or BAL immunoglobulin E (IgE) concentrations but did 
      produce a reduction in BAL and serum eotaxin concentrations (p < .05) at 6 h post 
      antigen challenge. This study shows that administration of an anti-IL-13 mAb was 
      well tolerated in both normal and allergic asthmatic macaques and that serum 
      eotaxin concentrations may be a useful early in vivo marker for evaluating IL-13 
      inhibition in patients with asthma.
FAU - Martin, Pauline L
AU  - Martin PL
AD  - Centocor Research and Development Inc., Radnor, Pennsylvania 19087, USA. 
      pmarti27@cntus.jnj.com
FAU - Fisher, Dusti
AU  - Fisher D
FAU - Glass, William
AU  - Glass W
FAU - O'Neil, Karyn
AU  - O'Neil K
FAU - Das, Anuk
AU  - Das A
FAU - Martin, Elise C
AU  - Martin EC
FAU - Li, Li
AU  - Li L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Int J Toxicol
JT  - International journal of toxicology
JID - 9708436
RN  - 0 (Anti-Asthmatic Agents)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Chemokines, CC)
RN  - 0 (Interleukin-13)
RN  - 0 (Interleukin-13 Receptor alpha1 Subunit)
RN  - 0 (Interleukin-13 Receptor alpha2 Subunit)
RN  - 0 (Recombinant Proteins)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (STAT6 protein, human)
SB  - IM
MH  - Animals
MH  - *Anti-Asthmatic Agents/adverse effects/pharmacology/therapeutic use
MH  - *Antibodies, Monoclonal/adverse effects/pharmacology/therapeutic use
MH  - Asthma/blood/*drug therapy/immunology
MH  - Bronchoalveolar Lavage Fluid/cytology/immunology
MH  - Chemokines, CC/blood/immunology
MH  - Disease Models, Animal
MH  - Drug Evaluation, Preclinical
MH  - Eosinophils/cytology
MH  - Humans
MH  - Injections, Intravenous
MH  - Interleukin-13/blood/*immunology
MH  - Interleukin-13 Receptor alpha1 Subunit/immunology
MH  - Interleukin-13 Receptor alpha2 Subunit/immunology
MH  - Macaca
MH  - Phosphorylation
MH  - Protein Binding
MH  - Recombinant Proteins/adverse effects/pharmacology/therapeutic use
MH  - STAT6 Transcription Factor/metabolism
EDAT- 2008/11/28 09:00
MHDA- 2009/01/31 09:00
CRDT- 2008/11/28 09:00
PHST- 2008/11/28 09:00 [pubmed]
PHST- 2009/01/31 09:00 [medline]
PHST- 2008/11/28 09:00 [entrez]
AID - 906041188 [pii]
AID - 10.1080/10915810802430509 [doi]
PST - ppublish
SO  - Int J Toxicol. 2008 Sep-Oct;27(5):351-8. doi: 10.1080/10915810802430509.