Andrea Bree, BS, Franklin J

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Presentation transcript:

IL-13 blockade reduces lung inflammation after Ascaris suum challenge in cynomolgus monkeys Andrea Bree, BS, Franklin J. Schlerman, BS, Michael Wadanoli, DVM, Lioudmila Tchistiakova, PhD, Kimberly Marquette, BS, Xiang- Yang Tan, MD, PhD, Bruce A. Jacobson, PhD, Angela Widom, MS, Timothy A. Cook, BS, Nancy Wood, BS, Suresh Vunnum, PhD, Rustem Krykbaev, PhD, Xin Xu, PhD, Debra D. Donaldson, MD, Samuel J. Goldman, PhD, Joseph Sypek, PhD, Marion T. Kasaian, PhD Journal of Allergy and Clinical Immunology Volume 119, Issue 5, Pages 1251-1257 (May 2007) DOI: 10.1016/j.jaci.2007.02.009 Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 1 Comparison of primate IL-13 amino acid sequences. The human (U31120) and cynomolgus monkey (DQ679797) amino acid sequences are 94% identical. Amino acid differences are shaded. Potential N-linked glycosylation sites are boxed. The R110Q polymorphism is indicated by an asterisk. The arrow indicates the N-terminus of the mature protein. Accession numbers are as follows: chimpanzee, AY480012; Pere David's macaque, AY849927; rhesus monkey, AY244790; and pigtailed macaque, DQ645391. The owl monkey partial sequence was reported in Bost et al.14 Journal of Allergy and Clinical Immunology 2007 119, 1251-1257DOI: (10.1016/j.jaci.2007.02.009) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 2 Cynomolgus monkey IL-13 has bioactivity and can be neutralized with antibodies. A, IL-13–induced CD23 expression on primary human monocytes. B, IL-13–induced STAT6 phosphorylation in HT-29. A half-maximal concentration of human (open symbols) or NHP (solid symbols) IL-13 was combined with the indicated concentration of mAb13.2 (C) or IMA-638 (D) in the STAT6 phosphorylation assay. Journal of Allergy and Clinical Immunology 2007 119, 1251-1257DOI: (10.1016/j.jaci.2007.02.009) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 3 Anti–IL-13 antibody reduced total BAL inflammation in response to A suum challenge. Animals were given IVIG or saline (control), dexamethasone (DEX), or anti–IL-13 (mAb13.2 or IMA-638). Twenty-four hours later, they were challenged with A suum antigen. BAL fluid was collected 24 hours after the challenge. A, Total cells; B, eosinophils; C, neutrophils; D, monocytes/macrophages. Median values are indicated. P values were determined by using the 2-tailed t test. Journal of Allergy and Clinical Immunology 2007 119, 1251-1257DOI: (10.1016/j.jaci.2007.02.009) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions

Fig 4 Anti-IL-13 reduces BAL chemokine levels after A suum challenge. Animals were given IVIG or saline (control), dexamethasone (DEX), or anti-IL-13 (mAb13.2 or IMA-638). Twenty-four hours later, they were challenged with A suum antigen. BAL fluid was collected 24 hours after the challenge and assayed for eotaxin (A; dashed line indicates limit of sensitivity, 7.8 pg/mL) and RANTES (B). P values were determined by using the paired 2-tailed t test. Journal of Allergy and Clinical Immunology 2007 119, 1251-1257DOI: (10.1016/j.jaci.2007.02.009) Copyright © 2007 American Academy of Allergy, Asthma & Immunology Terms and Conditions