Interleukin-4 inhibition for the treatment of Asthma

Biotherapeutic Approaches to Asthma

Volumn , Issue , 2016, Pages 107-132

  Borish, Larry ^a   Steinke, John W ^a   Davidson, Bruce ^b   Shames, Richard S ^c   Agosti, Jan M ^d  

^a UNIVERSITY OF VIRGINIA HEALTH SYSTEM   (United States)

^b BAYER CORPORATION   (United States)

^c PROTEIN DESIGN LABS INC   (United States)

^d AMGEN INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 4944254616     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.3109/9780203908808-9     Document Type: Chapter

References (91)

1. Hsieh CS, Heimberger AB, Gold JS, O’Garra A, Murphy KM. Differential regulation of T helper phenotype development by interleukins 4 and 10 in an alpha beta T-cell-receptor transgenic system. Proc Natl Acad Sci USA 1992; 89:6065-6069.
2. Seder RA, Paul WE, Davis MM, Fazekas de St. Groth B. The presence of interleukin 4 during in vitro priming determines the lymphokine-producing potential of CD4+ T cells from T cell receptor transgenic mice. J Exp Med 1992; 176:1091-1098.
3. Ohara J, Paul WE. Up-regulation of interleukin 4/B-cell stimulatory factor 1 receptor expression. Proc Natl Acad Sci USA 1988; 85:8221-8225.
4. Kopf M, Le Gros G, Bachmann M, Lamers MC, Bluethmann H, Kohler G. Disruption of the murine IL-4 gene blocks Th2 cytokine responses. Nature 1993; 362:245-248.
5. Jutel M, Pichler WJ, Skrbic D, Urwyler A, Dahinden C, Muller UR. Bee venom immunotherapy results in decrease of IL-4 and IL-5 and increase of IFN-gamma secretion in specific allergen-stimulated T cell cultures. J Immunol 1995; 154:4187-4194.
6. Coffman RL, Ohara J, Bond MW, Carty J, Zlotnik A, Paul WE. B cell stimulatory factor- 1 enhances the IgE response of lipopolysaccharide-activated B cells. J Immunol 1986; 136:4538-4541.
7. Pawankar R, Okuda M, Yssel H, Okumura K, Ra C. Nasal mast cells in perennial allergic rhinitis exhibit increased expression of the Fc epsilon RI, CD40L, IL-4, and IL-13, and can induce IgE synthesis in B cells. J Clin Invest 1997; 99:1492-1499.
8. Zaitsu M, Hamasaki Y, Matsuo M, Kukita A, Tsuji K, Miyazaki M, Hayasaki R, Muro E, Yamamoto S, Kobayashi I, Ichimaru T, Kohashi O, Miyazaki S. New induction of leukotriene A(4) hydrolase by interleukin-4 and interleukin- 13 in human polymorphonuclear leukocytes. Blood 2000; 96:601-609.
9. Hsieh FH, Lam BK, Penrose JF, Austen KF, Boyce JA. T helper cell type 2 cytokines coordinately regulate immunoglobulin E-dependent cysteinyl leukotriene production by human cord blood-derived mast cells: Profound induction of leukotriene C(4) synthase expression by interleukin 4. J Exp Med 2001; 193:123-133.
10. Rola-Pleszczynski M, Thivierge M, Stankova J. Upregulation of CysLT1 receptor expression by Th2 cytokine in human monocytes and macrophages. J Allergy Clin Immunol 2001; 107:S63.
11. Moser R, Fehr J, Bruijnzeel PL. IL-4 controls the selective endothelium-driven transmigration of eosinophils from allergic individuals. J Immunol 1992; 149:1432-1438.
12. Hoontrakoon R, Kailey J, Bratton D. IL-4 and TNF-alpha synergize to enhance eosinophil survival. J Allergy Clin Immunol 1999; 103:A239.
13. Vella A, Teague TK, Ihle J, Kappler J, Marrack P. Interleukin 4 (IL-4) or IL-7 prevents the death of resting T cells: Stat-6 is probably not required for the effect of IL-4. J Exp Med 1997; 186:325-330.
14. Xie H, Seward RJ, Huber BT. Cytokine rescue from glucocorticoid induced apoptosis in T cells is mediated through inhibition of IkappaBalpha. Mol Immunol 1997; 34:987-994.
15. Leung DYM, Hamid Q, Vottero A, Szefler SJ, Surs W, Minshall E, Chrousos GP, Klemm DJ. Association of glucocorticoid insensitivity with increased expression of glucocorticoid receptor beta. J Exp Med 1997; 186:1567-1574.
16. DeKruyff RH, Fang Y, Umetsu DT. Corticosteroids enhance the capacity of macrophages to induce Th2 cytokine synthesis in CD4+ lymphocytes by inhibiting IL-12 production. J Immunol 1998; 160:2231-2237.
17. Dabbagh K, Takeyama K, Lee HM, Ueki IF, Lausier JA, Nadel JA. IL-4 induces mucin gene expression and goblet cell metaplasia in vitro and in vivo. J Immunol 1999; 162:6233-6237.
18. Lordon J, Bucchieri F, Richter A, Holloway J, Beghe B, Konstantinidis A, Buchanan D, Wilson S, Djukanovic R, Holgate S, Davies D. The combined effects of Der p allergen and IL-4 or IL-13 on cytokine release by bronchial epithelial cell cultures of allergic asthmatics. J Allergy Clin Immunol 2001; 107:S63.
19. Doucet C, Brouty-Boye D, Pottin-Clemenceau C, Jasmin C, Canonica GW, Azzarone B. IL-4 and IL-13 specifically increase adhesion molecule and inflammatory cytokine expression in human lung fibroblasts. Int Immunol 1998; 10:1421-1433.
20. Chakir J, Page N, Barbeau B, Bergeron C. Interleukin-4, a Th2 cytokine, stimulates collagen 1 promoter activity in asthmatic bronchial fibroblasts. J Allergy Clin Immunol 2001; 107:S37.
21. Izuhara K, Shirakawa T. Signal transduction via the interleukin-4 receptor and its correlation with atopy. Int J Mol Med 1999; 3:3-10.
22. Jiang H, Harris MB, Rothman P. IL-4/IL-13 signaling beyond JAK/STAT. J Allergy Clin Immunol 2000; 105:1063-1070.
23. Leonard WJ, Lin JX. Cytokine receptor signaling pathways. J Allergy Clin Immunol 2000; 105:877-888.
24. Donaldson DD, Whitters MJ, Fitz LJ, Neben TY, Finnerty H, Henderson SL, O’Hara RM, Beier DR, Turner KJ, Wood CR, Collins M. The murine IL-13 receptor alpha 2: Molecular cloning, characterization, and comparison with murine IL-13 receptor alpha 1. J Immunol 1998; 161:2317-2324.
25. Nelms K, Keegan AD, Zamorano J, Ryan JJ, Paul WE. The IL-4 receptor: Signaling mechanisms and biologic functions. Annu Rev Immunol 1999; 17:701-738.
26. Jacobson NG, Szabo SJ, Weber-Nordt RM, Zhong Z, Schreiber RD, Darnell JE Jr, Murphy KM. Interleukin 12 signaling in T helper type 1 (Th1) cells involves tyrosine phosphorylation of signal transducer and activator of transcription (Stat)3 and Stat4. J Exp Med 1995; 181:1755-1762.
27. Losman JA, Chen XP, Hilton D, Rothman P. Cutting edge: SOCS-1 is a potent inhibitor of IL-4 signal transduction. J Immunol 1999; 162:3770-3774.
28. Harris MB, Chang CC, Berton MT, Danial NN, Zhang J, Kuehner D, Ye BH, Kvatyuk M, Pandolfi PP, Cattoretti G, Dalla-Favera R, Rothman PB. Transcriptional repression of Stat6-dependent interleukin-4-induced genes by BCL-6: Specific regulation of iepsilon transcription and immunoglobulin E switching. Mol Cell Biol 1999; 19:7264-7275.
29. Borish L. Genetics of allergy and asthma. Ann Allergy Asthma Immunol 1999; 82:413-424, 424-426.
30. Gao P-S, Mao X-Q, Hopkin JM, Adra CN, Yang X, Shirakawa T. Functional significance of polymorphisms of the interleukin-4 and interleukin-13 receptors in allergic disease. Clin Exp Allergy 2000; 30:1672-1675.
31. Marsh DG, Neely JD, Breazeale DR, Ghosh B, Freidhoff LR, Ehrlich-Kautzky E, Schou C, Krishnaswamy G, Beaty TH. Linkage analysis of IL4 and other chromosome 5q31.1 markers and total serum immunoglobulin E concentrations. Science 1994; 264:1152-1156.
32. Meyers DA, Postma DS, Panhuysen CI, Xu J, Amelung PJ, Levitt RC, Bleecker ER. Evidence for a locus regulating total serum IgE levels mapping to chromosome 5. Genomics 1994; 23:464-470.
33. Postma DS, Bleecker ER, Amelung PJ, Holroyd KJ, Xu J, Panhuysen CI, Meyers DA, Levitt RC. Genetic susceptibility to asthma: Bronchial hyperresponsiveness coinherited with a major gene for atopy. N Engl J Med 1995; 333:894-900.
34. Noguchi E, Shibasaki M, Arinami T, Takeda K, Maki T, Miyamoto T, Kawashima T, Kobayashi K, Hamaguchi H. Evidence for linkage between asthma/atopy in childhood and chromosome 5q31-q33 in a Japanese population. Am J Respir Crit Care Med 1997; 156:1390-1393.
35. Borish L, Mascali JJ, Klinnert M, Leppert M, Rosenwasser LJ. SSC polymorphisms in interleukin genes. Hum Mol Gen 1994; 3:1710.
36. Rosenwasser LJ, Klemm DJ, Dresback JK, Inamura H, Mascali JJ, Klinnert M, Borish L. Promoter polymorphisms in the chromosome 5 gene cluster in asthma and atopy. Clin Exp Allergy 1995; 25:74-78; discussion 95-96.
37. Walley AJ, Cookson WO. Investigation of an interleukin-4 promoter polymorphism for associations with asthma and atopy. J Med Genet 1996; 33:689-692.
38. Rosenwasser LJ, Borish L. Genetics of atopy and asthma: The rationale behind promoter-based candidate gene studies (IL-4 and IL-10). Am J Respir Crit Care Med 1997; 156:S152-S155.
39. Burchard EG, Silverman EK, Rosenwasser LJ, Borish L, Yandava C, Pillari A, Weiss ST, Hasday J, Lilly CM, Ford JG, Drazen JM. Association between a sequence variant in the IL-4 gene promoter and FEV1 in asthma. Am J Respir Crit Care Med 1999; 160:919-922.
40. Boyer S, Pereira E, Plamer L, Rye J, Goldblatt J, Sanderson C, Le Souef PL. Confirmation of the presence of a polymorphism in the interleukin 4 promoter in an asthmatic cohort. Am J Respir Crit Care Med 1995; 151:A470.
41. Noguchi E, Shibasaki M, Arinami T, Takeda K, Yokouchi Y, Kawashima T, Yanagi H, Matsui A, Hamaguchi H. Association of asthma and the interleukin-4 promoter gene in Japanese. Clin Exp Allergy 1998; 28:449-453.
42. Dizier MH, Sandford A, Walley A, Philippi A, Cookson W, Demenais F. Indication of linkage of serum IgE levels to the interleukin-4 gene and exclusion of the contribution of the (_590 C to T) interleukin-4 promoter polymorphism to IgE variation. Genet Epidemiol 1999; 16:84-94.
43. Song Z, Casolaro V, Chen R, Georas SN, Monos D, Ono SJ. Polymorphic nucleotides within the human IL-4 promoter that mediate overexpression of the gene. J Immunol 1996; 156:424-429.
44. Daniels SE, Bhattacharrya S, James A, Leaves NI, Young A, Hill MR, Faux JA, Ryan GF, le Souef PN, Lathrop GM, Musk AW, Cookson WO. A genome-wide search for quantitative trait loci underlying asthma. Nature 1996; 383:247-250.
45. Deichmann KA, Heinzmann A, Forster J, Dischinger S, Mehl C, Brueggenolte E, Hildebrandt F, Moseler M, Kuehr J. Linkage and allelic association of atopy and markers flanking the IL4-receptor gene. Clin Exp Allergy 1998; 28:151-155.
46. Ober C, Cox NJ, Abney M, Di Rienzo A, Lander ES, Changyaleket B, Gidley H, Kurtz B, Lee J, Nance M, Pettersson A, Prescott J, Richardson A, Schlenker E, Summerhill E, Willadsen S, Parry R. Genome-wide search for asthma susceptibility loci in a founder population. The Collaborative Study on the Genetics of Asthma. Hum Mol Gen 1998; 7:1393-1398.
47. Ober C, Leavitt SA, Tsalenko A, Howard TD, Hoki DM, Daniel R, Newman DL, Wu X, Parry R, Lester LA, Solway J, Blumenthal M, King RA, Xu J, Meyers DA, Bleecker ER, Cox NJ. Variation in the interleukin 4-receptor alpha gene confers susceptibility to asthma and atopy in ethnically diverse populations. Am J Hum Genet 2000; 66:517-526.
48. Deichmann K, Bardutzky J, Forster J, Heinzmann A, Kuehr J. Common polymorphisms in the coding part of the IL4-receptor gene. Biochem Biophys Res Commun 1997; 231:696-697.
49. Hershey GKK, Friedrich MF, Esswein LA, Thomas ML, Chatila TA. The association of atopy with a gain-of-function mutation in the alpha subunit of the interleukin-4 receptor. N Engl J Med 1997; 337:1720-1725.
50. Mitsuyasu H, Izuhara K, Mao XQ, Gao PS, Arinobu Y, Enomoto T, Kawai M, Sasaki S, Dake Y, Hamasaki N, Shirakawa T, Hopkin JM. Ile50Val variant of IL4R alpha upregulates IgE synthesis and associates with atopic asthma [letter]. Nat Genet 1998; 19:119-120.
51. Mitsuyasu H, Yanagihara Y, Mao XQ, Gao PS, Arinobu Y, Ihara K, Takabayashi A, Hara T, Enomoto T, Sasaki S, Kawai M, Hamasaki N, Shirakawa T, Hopkin JM, Izuhara K. Cutting edge: Dominant effect of Ile50Val variant of the human IL-4 receptor alpha-chain in IgE synthesis. J Immunol 1999; 162:1227-1231.
52. Ryan JJ, McReynolds LJ, Keegan A, Wang LH, Garfein E, Rothman P, Nelms K, Paul WE. Growth and gene expression are predominantly controlled by distinct regions of the human IL-4 receptor. Immunity 1996; 4:123-132.
53. Wang HY, Paul WE, Keegan AD. IL-4 function can be transferred to the IL-2 receptor by tyrosine containing sequences found in the IL-4 receptor alpha chain. Immunity 1996; 4:113-121.
54. Ryan JJ, McReynolds LJ, Huang H, Nelms K, Paul WE. Characterization of a mobile Stat6 activation motif in the human IL-4 receptor. J Immunol 1998; 161:1811-1821.
55. Sandford AJ, Chagani T, Zhu S, Weir TD, Bai TR, Spinelli JJ, Fitzgerald JM, Behbehani NA, Tan WC, Pare PD. Polymorphisms in the IL4, IL4RA, and FCERIB genes and asthma severity. J Allergy Clin Immunol 2000; 106:135-140.
56. Noguchi E, Shibasaki M, Arinami T, Takeda K, Yokouchi Y, Kobayashi K, Imoto N, Nakahara S, Matsui A, Hamaguchi H. Lack of association of atopy/asthma and the interleukin-4 receptor alpha gene in Japanese. Clin Exp Allergy 1999; 29:228-233.
57. Wang HY, Shelburne CP, Zamorano J, Kelly AE, Ryan JJ, Keegan AD. Cutting edge: Effects of an allergy-associated mutation in the human IL-4R alpha (Q576R) on human IL-4-induced signal transduction. J Immunol 1999; 162:4385-4389.
58. Patuzzo C, Trabetti E, Malerba G, Martinati LC, Boner AL, Pescollderungg L, Zanoni G, Pignatti PF. No linkage or association of the IL-4R alpha gene Q576R mutation with atopic asthma in Italian families [letter]. J Med Genet 2000; 37:382-384.
59. Kruse S, Japha T, Tedner M, Sparholt SH, Forster J, Kuehr J, Deichmann KA. The polymorphisms S503P and Q576R in the interleukin-4 receptor alpha gene are associated with atopy and influence the signal transduction. Immunology 1999; 96:365-371.
60. Heinzmann A, Mao XQ, Akaiwa M, Kreomer RT, Gao PS, Ohshima K, Umeshita R, Abe Y, Braun S, Yamashita T, Roberts MH, Sugimoto R, Arima K, Arinobu Y, Yu B, Kruse S, Enomoto T, Dake Y, Kawai M, Shimazu S, Sasaki S, Adra CN, Kitaichi M, Inoue H, Yamauchi K, Tomichi N, Kurimoto F, Hamasaki N, Hopkin JM, Izuhara K, Shirakawa T, Deichmann KA. Genetic variants of IL-13 signalling and human asthma and atopy. Hum Mol Gen 2000; 9:549-559.
61. Shirakawa T, Li A, Dubowitz M, Dekker JW, Shaw AE, Faux JA, Ra C, Cookson WO, Hopkin JM. Association between atopy and variants of the beta subunit of the high-affinity immunoglobulin E receptor [see comments]. Nat Genet 1994; 7:125-129.
62. Gao PS, Mao XQ, Roberts MH, Arinobu Y, Akaiwa M, Enomoto T, Dake Y, Kawai M, Sasaki S, Hamasaki N, Izuhara K, Shirakawa T, Hopkin JM. Variants of STAT6 (signal transducer and activator of transcription 6) in atopic asthma [letter]. J Med Genet 2000; 37:380-382.
63. Adra CN, Gao PS, Mao XQ, Baron BW, Pauker S, Miki T, Shirakawa T, Hopkin JM. Variants of B cell lymphoma 6 (BCL6) and marked atopy [letter]. Clin Genet 1998; 54:362-364.
64. Coyle AJ, Le Gros G, Bertrand C, Tsuyuki S, Heusser CH, Kopf M, Anderson GP. Interleukin-4 is required for the induction of lung Th2 mucosal immunity. Am J Respir Cell Mol Biol 1995; 13:54-59.
65. Corry DB, Folkesson HG, Warnock ML, Erle DJ, Matthay MA, Wiener-Kronish JP, Locksley RM. Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway hyperreactivity. J Exp Med 1996; 183:109-117.
66. Renz H, Bradley K, Enssle K, Loader JE, Larsen GL, Gelfand EW. Prevention of the development of immediate hypersensitivity and airway hyperresposiveness fol lowing in vivo treatment with soluble IL-4 receptor. Int Arch Allergy Immunol 1996; 109:167-176.
67. Henderson WR Jr, Chi EY, Maliszewski CR. Soluble IL-4 receptor inhibits airway inflammation following allergen challenge in a mouse model of asthma. J Immunol 2000; 164:1086-1095.
68. Walker C, Bauer W, Braun RK, Menz G, Braun P, Schwarz F, Hansel TT, Villiger B. Activated T cells and cytokines in bronchoalveolar lavages from patients with various lung diseases associated with eosinophilia. Am J Respir Crit Care Med 1994; 150:1038-1048.
69. Daher S, Santos LM, Sole D, De Lima MG, Naspitz CK, Musatti CC. Interleukin-4 and soluble CD23 serum levels in asthmatic atopic children. J Invest Allergol Clin Immunol 1995; 5:251-254.
70. Robinson DS, Hamid Q, Ying S, Tsicopoulos A, Barkans J, Bentley AM, Corrigan C, Durham SR, Kay AB. Predominant TH2-like bronchoalveolar T-lymphocyte population in atopic asthma. N Engl J Med 1992; 326:298-304.
71. Leonard C, Tormey V, Burke C, Poulter LW. Allergen-induced cytokine production in atopic disease and its relationship to disease severity. Am J Respir Crit Care Med 1997; 17:368-375.
72. Smart J, Horak E, Roberts M, Lanigan A, Kemp A. Melbourne study of childhood asthma: Allergen-specific cytokine responses according to clinical outcome at 42 years. J Allergy Clin Immunol 2001; 107:S64.
73. Shi HZ, Deng JM, Xu H, Nong ZX, Xiao CQ, Liu ZM, Qin SM, Jiang HX, Liu GN, Chen YQ. Effect of inhaled interleukin-4 on airway hyperreactivity in asthmatics. Am J Respir Crit Care Med 1998; 157:1818-1821.
74. Parronchi P, De Carli M, Manetti R, Simonelli C, Piccinni MP, Macchia D, Maggi E, Del Prete G, Ricci M, Romagnani S. Aberrant interleukin (IL)-4 and IL-5 production in vitro by CD4+ helper T cells from atopic subjects. Eur J Immunol 1992; 22:1615-1620.
75. Chan SC, Brown MA, Willcox TM, Li SH, Stevens SR, Tara D, Hanifin JM. Abnormal IL-4 gene expression by atopic dermatitis T lymphocytes is reflected in altered nuclear protein interactions with IL-4 transcriptional regulatory element. J Invest Dermatol 1996; 106:1131-1136.
76. Piccinni MP, Beloni L, Giannarini L, Livi C, Scarselli G, Romagnani S, Maggi E. Abnormal production of T helper 2 cytokines interleukin-4 and interleukin-5 by T cells from newborns with atopic parents. Eur J Immunol 1996; 26:2293-2298.
77. Grunewald SM, Werthmann A, Schnarr B, Klein CE, Brocker EB, Mohrs M, Brombacher F, Sebald W, Duschl A. An antagonistic IL-4 mutant prevents type I allergy in the mouse: Inhibition of the IL-4/IL-13 receptor system completely abrogates humoral immune response to allergen and development of allergic symptoms in vivo. J Immunol 1998; 160:4004-4009.
78. Benson M, Strannegard IL, Wennergren G, Strannegard O. Cytokines in nasal fluids from school children with seasonal allergic rhinitis. Pediatr Allergy Immunol 1997; 8:143-149.
79. Borish LC, Nelson HS, Lanz MJ, Claussen L, Whitmore JB, Agosti JM, Garrison L. Interleukin-4 receptor in moderate atopic asthma. A phase I/II randomized, placebocontrolled trial. Am J Respir Crit Care Med 1999; 160:1816-1823.
80. Borish L, Nelson H, Corren J, Bensch G, Busse W, Whitmore J, Agosti J. Efficacy of soluble interleukin-4 receptor for the treatment of adults with asthma. J Allergy Clin Immunol 2001; 107:963-970.
81. Snell N. Interleukin-4 as a therapeutic target in allergic disorders. Curr Opin Anti-Inflam Immunomod Invest Drug 2000; 2:99.
82. Shanafelt M, Harris P, Neyer L, Moy J, Barrientos J, Gundel R. Mechanism of action of an IL-4 receptor antagonist (BAY 16-9996) in the primate model of asthma. Am J Respir Crit Care Med 2000; 161:A201.
83. Harris P, Lindell D, Fitch N, Gundel R. The IL-4 receptor antagonist (BAY 16-9996) reverses airway hyperresponsiveness in a primate model of asthma. Am J Respir Crit Care Med 1999; 159:A230.
84. Fitch N, Harris P, Lindell D. Evaluation of a dual IL-4 and IL-13 receptor antagonist in a primate model of asthma. Submitted for publication.
85. Gundel R, Morton M, Bowden A, Fitch N, Shanafelt M, Shanafelt A, Wetzel G, Moy J, Gibbons J, Terrell T. Preclinical evaluation of BAY 16-9996 a dual IL-4/ IL-13 receptor antagonist. Eur Respir J 2000; 16:564.
86. Shames R, Vexler V, Lane N, McClellan M, Shi J, Keller S, Young D, Nieman R, Hart T. The safety and pharmacokinetics of SSB240683 (anti-IL-4 humanized monoclonal antibody) in patients with mild to moderate asthma. J Allergy Clin Immunol 2001; 107:S317.
87. Tocker J, Raminfar L, Barone C. Effects of an antibody to IL-4R in a mouse asthma model. Am J Respir Crit Care Med 2001; 163:A523.
88. Hansen G, Berry G, DeKruyff RH, Umetsu DT. Allergen-specific Th1 cells fail to counterbalance Th2 cell-induced airway hyperreactivity but cause severe airway inflammation. J Clin Invest 1999; 103:175-183.
89. Finkelman FD, Shea-Donohue T, Goldhill J, Sullivan CA, Morris SC, Madden KB, Gause WC, Urban JF Jr. Cytokine regulation of host defense against parasitic gastrointestinal nematodes: Lessons from studies with rodent models. Annu Rev Immunol 1997; 15:505-533.
90. Urban JFJ, Noben-Trauth N, Donaldson D, Madden KB, Morris SC, Collins M, Finkelman FD. IL-13, IL-4R alpha and Stat6 are required for expulsion of the gastrointestinal nematode parasite Nippostrongylus brasiliensis. Immunity 1998; 8:255-264.
91. Baron BW, Billstrand C, Madronero L, McKeithan TW. HindIII polymorphism in the BCL6 gene. Hum Mol Gen 1993; 2:1513.