PJ Mauser, AM Pitman, X Fernandez, SK Foran, GK Adams 3rd, W Kreutner, RW Egan and RW Chapman
Department of Allergy, Schering-Plough Research Institute, Kenilworth, NJ 07033-0539, USA.

To investigate the role of interleukin-5 (IL-5) on airway hyperreactivity and pulmonary inflammation in nonhuman primate airways, the effect of a neutralizing monoclonal antibody to murine IL-5 (TRFK- 5) was investigated in a cynomolgus monkey model of allergic asthma. Anesthetized Ascaris-sensitive monkeys underwent bronchoalveolar lavage (BAL) to assess the granulocyte content of this fluid before and 24 h after aerosolized Ascaris suum extract inhalation. Airway reactivity was assessed by the concentration of inhaled histamine required to produce a 40% reduction in dynamic lung compliance (Cdyn40). Exposure to A. suum extract produced an increase in airway reactivity (Cdyn40 = 0.065 +/- 0.024% before Ascaris; Cdyn40 = 0.014 +/- 0.004% after Ascaris) and an inflammatory reaction in the airways characterized by an increase in BAL eosinophils (0.05 +/- 0.03 x 10(3) cells/ml before Ascaris; 176 +/- 76 x 10(3) cells/ml after Ascaris) and neutrophils (3 +/- 1 x 10(3) cells/ml before Ascaris; 406 +/- 211 x 10(3) cells/ml after Ascaris). In contrast, only small nonsignificant changes in airway reactivity and granulocyte influx into the BAL occurred after aerosolized saline as a sham challenge. When the monkeys were treated 1 h before Ascaris challenge with the TRFK-5 antibody (0.3 mg/kg, intravenously), there was no increase in airway reactivity after Ascaris challenge (Cdyn40 = 0.032 +/- 0.016% before Ascaris; Cdyn40 = 0.217 +/- 0.196% after Ascaris) and there were only small increases in the number of eosinophils and neutrophils in the BAL after Ascaris challenge. The inhibition of this pulmonary eosinophilia and bronchial hyperresponsiveness by TRFK-5 was seen for up to 3 mo after treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

This article has been cited by other articles:

				M. Mellado, A. M. de Ana, L. Gomez, C. Martinez-A, and J. M. Rodriguez-Frade Chemokine Receptor 2 Blockade Prevents Asthma in a Cynomolgus Monkey Model J. Pharmacol. Exp. Ther., February 1, 2008; 324(2): 769 - 775. [Abstract] [Full Text] [PDF]

				P. Flood-Page, C. Swenson, I. Faiferman, J. Matthews, M. Williams, L. Brannick, D. Robinson, S. Wenzel, W. Busse, T. T. Hansel, et al. A Study to Evaluate Safety and Efficacy of Mepolizumab in Patients with Moderate Persistent Asthma Am. J. Respir. Crit. Care Med., December 1, 2007; 176(11): 1062 - 1071. [Abstract] [Full Text] [PDF]

				D. J. Tumes, J. Cormie, M. G. Calvert, K. Stewart, C. Nassenstein, A. Braun, P. S. Foster, and L. A. Dent Strain-dependent resistance to allergen-induced lung pathophysiology in mice correlates with rate of apoptosis of lung-derived eosinophils J. Leukoc. Biol., June 1, 2007; 81(6): 1362 - 1373. [Abstract] [Full Text] [PDF]

				N. G. Verbout, J. K. Lorton, D. B. Jacoby, and A. D. Fryer Atropine pretreatment enhances airway hyperreactivity in antigen-challenged guinea pigs through an eosinophil-dependent mechanism Am J Physiol Lung Cell Mol Physiol, May 1, 2007; 292(5): L1126 - L1135. [Abstract] [Full Text] [PDF]

				E. Lopez, V. del Pozo, T. Miguel, B. Sastre, C. Seoane, E. Civantos, E. Llanes, M. L. Baeza, P. Palomino, B. Cardaba, et al. Inhibition of Chronic Airway Inflammation and Remodeling by Galectin-3 Gene Therapy in a Murine Model J. Immunol., February 1, 2006; 176(3): 1943 - 1950. [Abstract] [Full Text] [PDF]

				D. L. Chou, B. L. Daugherty, E. K. McKenna, W. M. Hsu, N. K. Tyler, C. G. Plopper, D. M. Hyde, E. S. Schelegle, L. J. Gershwin, and L. A. Miller Chronic Aeroallergen during Infancy Enhances Eotaxin-3 Expression in Airway Epithelium and Nerves Am. J. Respir. Cell Mol. Biol., July 1, 2005; 33(1): 1 - 8. [Abstract] [Full Text] [PDF]

				R. L. Coffman and E. M. Hessel Nonhuman primate models of asthma J. Exp. Med., June 20, 2005; 201(12): 1875 - 1879. [Abstract] [Full Text] [PDF]

				R. K. Kumar, C. Herbert, D. C. Webb, L. Li, and P. S. Foster Effects of Anticytokine Therapy in a Mouse Model of Chronic Asthma Am. J. Respir. Crit. Care Med., November 15, 2004; 170(10): 1043 - 1048. [Abstract] [Full Text] [PDF]

				J. H. Edwan, G. Perry, J. E. Talmadge, and D. K. Agrawal Flt-3 Ligand Reverses Late Allergic Response and Airway Hyper-Responsiveness in a Mouse Model of Allergic Inflammation J. Immunol., April 15, 2004; 172(8): 5016 - 5023. [Abstract] [Full Text] [PDF]

				M. R. Van Scott, J. L. Hooker, D. Ehrmann, Y. Shibata, C. Kukoly, K. Salleng, G. Westergaard, A. Sandrasagra, and J. Nyce Dust mite-induced asthma in cynomolgus monkeys J Appl Physiol, April 1, 2004; 96(4): 1433 - 1444. [Abstract] [Full Text] [PDF]

				M. Castro, S. R. Bloch, M. V. Jenkerson, S. DeMartino, D. L. Hamilos, R. B. Cochran, X. E. L. Zhang, H. Wang, J. P. Bradley, K. B. Schechtman, et al. Asthma Exacerbations after Glucocorticoid Withdrawal Reflects T Cell Recruitment to the Airway Am. J. Respir. Crit. Care Med., April 1, 2004; 169(7): 842 - 849. [Abstract] [Full Text] [PDF]

				K. Matsumoto, M. Terakawa, K. Miura, S. Fukuda, T. Nakajima, and H. Saito Extremely Rapid and Intense Induction of Apoptosis in Human Eosinophils by Anti-CD30 Antibody Treatment In Vitro J. Immunol., February 15, 2004; 172(4): 2186 - 2193. [Abstract] [Full Text] [PDF]

				S. Myou, A. R. Leff, S. Myo, E. Boetticher, J. Tong, A. Y. Meliton, J. Liu, N. M. Munoz, and X. Zhu Blockade of Inflammation and Airway Hyperresponsiveness in Immune-sensitized Mice by Dominant-Negative Phosphoinositide 3-Kinase-TAT J. Exp. Med., November 17, 2003; 198(10): 1573 - 1582. [Abstract] [Full Text] [PDF]

				S. Myou, X. Zhu, S. Myo, E. Boetticher, A. Y. Meliton, J. Liu, N. M. Munoz, and A. R. Leff Blockade of Airway Inflammation and Hyperresponsiveness by HIV-TAT-Dominant Negative Ras J. Immunol., October 15, 2003; 171(8): 4379 - 4384. [Abstract] [Full Text] [PDF]

				M. J. Holtzman Drug Development for Asthma Am. J. Respir. Cell Mol. Biol., August 1, 2003; 29(2): 163 - 171. [Abstract] [Full Text] [PDF]

				J. C. Kips, B. J. O'Connor, S. J. Langley, A. Woodcock, H. A. M. Kerstjens, D. S. Postma, M. Danzig, F. Cuss, and R. A. Pauwels Effect of SCH55700, a Humanized Anti-Human Interleukin-5 Antibody, in Severe Persistent Asthma: A Pilot Study Am. J. Respir. Crit. Care Med., June 15, 2003; 167(12): 1655 - 1659. [Abstract] [Full Text] [PDF]

				B. Gregory, A. Kirchem, S. Phipps, P. Gevaert, C. Pridgeon, S. M. Rankin, and D. S. Robinson Differential Regulation of Human Eosinophil IL-3, IL-5, and GM-CSF Receptor {alpha}-Chain Expression by Cytokines: IL-3, IL-5, and GM-CSF Down-Regulate IL-5 Receptor {alpha} Expression with Loss of IL-5 Responsiveness, but Up-Regulate IL-3 Receptor {alpha} Expression J. Immunol., June 1, 2003; 170(11): 5359 - 5366. [Abstract] [Full Text] [PDF]

				C. Buttner, A. Lun, T. Splettstoesser, G. Kunkel, and H. Renz Monoclonal anti-interleukin-5 treatment suppresses eosinophil but not T-cell functions Eur. Respir. J., May 1, 2003; 21(5): 799 - 803. [Abstract] [Full Text] [PDF]

				W. W. Busse and E. A. E. B. Kelly Is the Eosinophil a "Humpty Dumpty" Cell in Asthma? Am. J. Respir. Crit. Care Med., January 15, 2003; 167(2): 102 - 103. [Full Text] [PDF]

				P. T. Flood-Page, A. N. Menzies-Gow, A. B. Kay, and D. S. Robinson Eosinophil's Role Remains Uncertain as Anti-Interleukin-5 only Partially Depletes Numbers in Asthmatic Airway Am. J. Respir. Crit. Care Med., January 15, 2003; 167(2): 199 - 204. [Abstract] [Full Text] [PDF]

				J. G. Martin, M. Suzuki, K. Maghni, R. Pantano, D. Ramos-Barbon, D. Ihaku, F. Nantel, D. Denis, Q. Hamid, and W. S. Powell The Immunomodulatory Actions of Prostaglandin E2 on Allergic Airway Responses in the Rat J. Immunol., October 1, 2002; 169(7): 3963 - 3969. [Abstract] [Full Text] [PDF]

				L. Zhang, M. P. Soares, Y. Guan, S. Matheravidathu, R. Wnek, K. E. Johnson, A. Meisher, S. A. Iliff, J. S. Mudgett, M. S. Springer, et al. Functional Expression and Characterization of Macaque C-C Chemokine Receptor 3 (CCR3) and Generation of Potent Antagonistic Anti-macaque CCR3 Monoclonal Antibodies J. Biol. Chem., September 6, 2002; 277(37): 33799 - 33810. [Abstract] [Full Text] [PDF]

				B. Morse, J. P. Sypek, D. D. Donaldson, K. J. Haley, and C. M. Lilly Effects of IL-13 on airway responses in the guinea pig Am J Physiol Lung Cell Mol Physiol, January 1, 2002; 282(1): L44 - L49. [Abstract] [Full Text] [PDF]

				E L J van Rensen, R G Stirling, J Scheerens, K Staples, P J Sterk, P J Barnes, and K F Chung Evidence for systemic rather than pulmonary effects of interleukin-5 administration in asthma Thorax, December 1, 2001; 56(12): 935 - 940. [Abstract] [Full Text] [PDF]

				M. Yang, S. P. Hogan, P. J. Henry, K. I. Matthaei, A. N. J. McKenzie, I. G. Young, M. E. Rothenberg, and P. S. Foster Interleukin-13 Mediates Airways Hyperreactivity through the IL-4 Receptor-Alpha Chain and STAT-6 Independently of IL-5 and Eotaxin Am. J. Respir. Cell Mol. Biol., October 1, 2001; 25(4): 522 - 530. [Abstract] [Full Text] [PDF]

				M. Hertz, S. Mahalingam, I. Dalum, S. Klysner, J. Mattes, A. Neisig, S. Mouritsen, P. S. Foster, and A. Gautam Active Vaccination Against IL-5 Bypasses Immunological Tolerance and Ameliorates Experimental Asthma J. Immunol., October 1, 2001; 167(7): 3792 - 3799. [Abstract] [Full Text] [PDF]

				P.J. Barnes Cytokine modulators as novel therapies for airway disease Eur. Respir. J., July 2, 2001; 18(34_suppl): 67S - 77s. [Abstract] [Full Text] [PDF]

				K. G. Tournoy, J. C. Kips, and R. A. Pauwels The Allergen-Induced Airway Hyperresponsiveness in a Human-Mouse Chimera Model of Asthma Is T Cell and IL-4 and IL-5 Dependent J. Immunol., June 1, 2001; 166(11): 6982 - 6991. [Abstract] [Full Text] [PDF]

				C. LAMBLIN, F. BOLARD, P. GOSSET, A. TSICOPOULOS, T. PEREZ, J. DARRAS, A. JANIN, A. B. TONNEL, Q. HAMID, and B. WALLAERT Bronchial Interleukin-5 and Eotaxin Expression in Nasal Polyposis . Relationship with (A)symptomatic Bronchial Hyperresponsiveness Am. J. Respir. Crit. Care Med., April 1, 2001; 163(5): 1226 - 1232. [Abstract] [Full Text]

				E. Lach-Trifilieff, R. A. McKay, B. P. Monia, J. G. Karras, and C. Walker In Vitro and In Vivo Inhibition of Interleukin (IL)-5-Mediated Eosinopoiesis by Murine IL-5R{alpha} Antisense Oligonucleotide Am. J. Respir. Cell Mol. Biol., February 1, 2001; 24(2): 116 - 122. [Abstract] [Full Text]

				A.B. Kay Allergy and Allergic Diseases- Second of Two Parts N. Engl. J. Med., January 11, 2001; 344(2): 109 - 113. [Full Text] [PDF]

				M. Tomaki, L.-L. Zhao, J. Lundahl, M. Sjostrand, M. Jordana, A. Linden, P. O'Byrne, and J. Lotvall Eosinophilopoiesis in A Murine Model of Allergic Airway Eosinophilia: Involvement of Bone Marrow IL-5 and IL-5 Receptor {alpha} J. Immunol., October 1, 2000; 165(7): 4040 - 4050. [Abstract] [Full Text] [PDF]

				E. Lach-Trifilieff, K. Menear, E. Schweighoffer, V. L. J. Tybulewicz, and C. Walker Syk-deficient eosinophils show normal interleukin-5-mediated differentiation, maturation, and survival but no longer respond to Fcgamma R activation Blood, October 1, 2000; 96(7): 2506 - 2510. [Abstract] [Full Text] [PDF]

				C. M. Evans, K. E. Belmonte, R. W. Costello, D. B. Jacoby, G. J. Gleich, and A. D. Fryer Substance P-induced airway hyperreactivity is mediated by neuronal M2 receptor dysfunction Am J Physiol Lung Cell Mol Physiol, September 1, 2000; 279(3): L477 - L486. [Abstract] [Full Text] [PDF]

				M. R. van Scott, J. P. Justice, J. F. Bradfield, E. Enright, A. Sigounas, and S. Sur IL-10 reduces Th2 cytokine production and eosinophilia but augments airway reactivity in allergic mice Am J Physiol Lung Cell Mol Physiol, April 1, 2000; 278(4): L667 - L674. [Abstract] [Full Text] [PDF]

				J. S. Wild, A. Sigounas, N. Sur, M. S. Siddiqui, R. Alam, M. Kurimoto, and S. Sur IFN-{gamma}-Inducing Factor (IL-18) Increases Allergic Sensitization, Serum IgE, Th2 Cytokines, and Airway Eosinophilia in a Mouse Model of Allergic Asthma J. Immunol., March 1, 2000; 164(5): 2701 - 2710. [Abstract] [Full Text] [PDF]

				J. Tavernier, J. Van der Heyden, A. Verhee, G. Brusselle, X. Van Ostade, J. Vandekerckhove, J. North, S. M. Rankin, A. B. Kay, and D. S. Robinson Interleukin 5 regulates the isoform expression of its own receptor alpha -subunit Blood, March 1, 2000; 95(5): 1600 - 1607. [Abstract] [Full Text] [PDF]

				J. Zhang, R. Kuvelkar, N. J. Murgolo, S. S. Taremi, C.-C. Chou, P. Wang, M. M. Billah, and R. W. Egan Mapping and characterization of the epitope(s) of Sch 55700, a humanized mAb, that inhibits human IL-5 Int. Immunol., December 1, 1999; 11(12): 1935 - 1944. [Abstract] [Full Text] [PDF]

				A. Mori, O. Kaminuma, K. Miyazawa, K. Ogawa, H. Okudaira, and K. Akiyama p38 Mitogen-Activated Protein Kinase Regulates Human T Cell IL-5 Synthesis J. Immunol., November 1, 1999; 163(9): 4763 - 4771. [Abstract] [Full Text] [PDF]

				B. L. Yost, G. J. Gleich, and A. D. Fryer Ozone-induced hyperresponsiveness and blockade of M2 muscarinic receptors by eosinophil major basic protein J Appl Physiol, October 1, 1999; 87(4): 1272 - 1278. [Abstract] [Full Text] [PDF]

				Q. Sun, K. Jones, B. McClure, B. Cambareri, B. Zacharakis, P.O. Iversen, F. Stomski, J.M. Woodcock, C.J. Bagley, R. D'Andrea, et al. Simultaneous Antagonism of Interleukin-5, Granulocyte-Macrophage Colony-Stimulating Factor, and Interleukin-3 Stimulation of Human Eosinophils by Targetting the Common Cytokine Binding Site of Their Receptors Blood, September 15, 1999; 94(6): 1943 - 1951. [Abstract] [Full Text] [PDF]

				E. HAMELMANN, G. CIESLEWICZ, J. SCHWARZE, T. ISHIZUKA, A. JOETHAM, C. HEUSSER, and E. W. GELFAND Anti-interleukin 5 But Not Anti-IgE Prevents Airway Inflammation and Airway Hyperresponsiveness Am. J. Respir. Crit. Care Med., September 1, 1999; 160(3): 934 - 941. [Abstract] [Full Text]

				K F Chung and P J Barnes Cytokines in asthma Thorax, September 1, 1999; 54(9): 825 - 857. [Full Text]

				T. Hisada, P. G. Hellewell, M. M. Teixeira, M. G. K. Malm, M. Salmon, T.-J. Huang, and K. Fan Chung alpha 4 Integrin-Dependent Eotaxin Induction of Bronchial Hyperresponsiveness and Eosinophil Migration in Interleukin-5 Transgenic Mice Am. J. Respir. Cell Mol. Biol., May 1, 1999; 20(5): 992 - 1000. [Abstract] [Full Text]

				C. G. Garlisi, T. T. Kung, P. Wang, M. Minnicozzi, S. P. Umland, R. W. Chapman, D. Stelts, Y. Crawley, A. Falcone, J. G. Myers, et al. Effects of Chronic Anti-Interleukin-5 Monoclonal Antibody Treatment in a Murine Model of Pulmonary Inflammation Am. J. Respir. Cell Mol. Biol., February 1, 1999; 20(2): 248 - 255. [Abstract] [Full Text]

				H. MISHIMA, M. HOJO, A. WATANABE, Q. A. HAMID, and J. G. MARTIN CD4+ T Cells Can Induce Airway Hyperresponsiveness to Allergen Challenge in the Brown Norway Rat Am. J. Respir. Crit. Care Med., December 1, 1998; 158(6): 1863 - 1870. [Abstract] [Full Text] [PDF]

				P. J. Barnes, K. F. Chung, and C. P. Page Inflammatory Mediators of Asthma: An Update Pharmacol. Rev., December 1, 1998; 50(4): 515 - 596. [Abstract] [Full Text] [PDF]

				A. D. FRYER and D. B. JACOBY Muscarinic Receptors and Control of Airway Smooth Muscle Am. J. Respir. Crit. Care Med., November 1, 1998; 158(2007): S154 - S160. [Abstract] [Full Text] [PDF]

				C. Walker, J. Checkel, S. Cammisuli, P. J. Leibson, and G. J. Gleich IL-5 Production by NK Cells Contributes to Eosinophil Infiltration in a Mouse Model of Allergic Inflammation J. Immunol., August 15, 1998; 161(4): 1962 - 1969. [Abstract] [Full Text] [PDF]

				M. E. Rothenberg Eosinophilia N. Engl. J. Med., May 28, 1998; 338(22): 1592 - 1600. [Full Text] [PDF]

				S. P. Umland, S. Razac, H. Shah, D. Kyle Nahrebne, R. W. Egan, and M. Motasim Billah Interleukin-5 mRNA Stability in Human T Cells Is Regulated Differently than Interleukin-2, Interleukin-3, Interleukin-4, Granulocyte/Macrophage Colony-stimulating Factor, and Interferon-gamma Am. J. Respir. Cell Mol. Biol., May 1, 1998; 18(5): 631 - 642. [Abstract] [Full Text]

				L. J. WOOD, M. D. INMAN, R. M. WATSON, R. FOLEY, J. A. DENBURG, and P. M. O'BYRNE Changes in Bone Marrow Inflammatory Cell Progenitors after Inhaled Allergen in Asthmatic Subjects Am. J. Respir. Crit. Care Med., January 1, 1998; 157(1): 99 - 105. [Abstract] [Full Text] [PDF]

				J. B. Madwed and A. C. Jackson Determination of airway and tissue resistances after antigen and methacholine in nonhuman primates J Appl Physiol, November 1, 1997; 83(5): 1690 - 1696. [Abstract] [Full Text] [PDF]

				C. G. Garlisi, A. Falcone, J. A. Hey, T. M. Paster, X. Fernandez, C. A. Rizzo, M. Minnicozzi, H. Jones, M. Motasim Billah, R. W. Egan, et al. Airway Eosinophils, T Cells, Th2-Type Cytokine mRNA, and Hyperreactivity in Response to Aerosol Challenge of Allergic Mice with Previously Established Pulmonary Inflammation Am. J. Respir. Cell Mol. Biol., November 1, 1997; 17(5): 642 - 651. [Abstract] [Full Text]

				E. A. B. KELLY, R. R. RODRIGUEZ, W. W. BUSSE, and N. N. JARJOUR The Effect of Segmental Bronchoprovocation with Allergen on Airway Lymphocyte Function Am. J. Respir. Crit. Care Med., November 1, 1997; 156(5): 1421 - 1428. [Abstract] [Full Text]

				R. A. PAUWELS, G. J. BRUSSELLE, and J. C. KIPS Cytokine Manipulation in Animal Models of Asthma Am. J. Respir. Crit. Care Med., October 1, 1997; 156(4): S78 - S81. [Abstract] [Full Text] [PDF]

				M. HUMBERT, C. J. CORRIGAN, P. KIMMITT, S. J. TILL, A. BARRY KAY, and S. R. DURHAM Relationship between IL-4 and IL-5 mRNA Expression and Disease Severity in Atopic Asthma Am. J. Respir. Crit. Care Med., September 1, 1997; 156(3): 704 - 708. [Abstract] [Full Text] [PDF]

				E. HAMELMANN, J. SCHWARZE, K. TAKEDA, A. OSHIBA, G. L. LARSEN, C. G. IRVIN, and E. W. GELFAND Noninvasive Measurement of Airway Responsiveness in Allergic Mice Using Barometric Plethysmography Am. J. Respir. Crit. Care Med., September 1, 1997; 156(3): 766 - 775. [Abstract] [Full Text] [PDF]

				M. D. Edgerton, P. Graber, D. Willard, T. Consler, M. McKinnon, I. Uings, C. Y. Arod, F. Borlat, R. Fish, M. C. Peitsch, et al. Spatial Orientation of the alpha  and beta c Receptor Chain Binding Sites on Monomeric Human Interleukin-5 Constructs J. Biol. Chem., August 15, 1997; 272(33): 20611 - 20618. [Abstract] [Full Text] [PDF]

				F. G. Rolfe, J. E. Valentine, and W. A. Sewell Cyclosporin A and FK506 Reduce Interleukin-5 mRNA Abundance by Inhibiting Gene Transcription Am. J. Respir. Cell Mol. Biol., August 1, 1997; 17(2): 243 - 250. [Abstract] [Full Text]

				M. McKinnon, K. Page, I. J. Uings, M. Banks, D. Fattah, A. E.I. Proudfoot, P. Graber, C. Arod, R. Fish, T. N.C. Wells, et al. An Interleukin 5 Mutant Distinguishes between Two Functional Responses in Human Eosinophils J. Exp. Med., July 7, 1997; 186(1): 121 - 129. [Abstract] [Full Text] [PDF]

				H.-Z. SHI, C.-Q. XIAO, D. ZHONG, S.-M. QIN, Y. LIU, G.-R. LIANG, H. XU, Y.-Q. CHEN, X.-M. LONG, and Z.-F. XIE Effect of Inhaled Interleukin-5 on Airway Hyperreactivity and Eosinophilia in Asthmatics Am. J. Respir. Crit. Care Med., January 1, 1997; 157(1): 204 - 209. [Abstract] [Full Text]

B. P. England, P. Balasubramanian, I. Uings, S. Bethell, M.-J. Chen, P. J. Schatz, Q. Yin, Y.-F. Chen, E. A. Whitehorn, A. Tsavaler, et al. A potent dimeric peptide antagonist of