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Laboratory of Experimental Immunology, Division of Basic Sciences, National Cancer Institute, Frederick Cancer and Research Development Center, Frederick, MD 21702
IL-13 and IL-4 have similar biological activities and are
characteristic of cytokines expressed by Th2 cells. In contrast, IL-12
and IL-18 have been shown to be strong cofactors for Th1 cell
development. In this study, we found strong induction of IL-13 mRNA and
protein by IL-2 + IL-18 in NK and T cells. In contrast, IL-12 did not
enhance the IL-13 production induced by IL-2 alone. Moreover, IL-13
mRNA and protein expression induced by IL-2 + IL-18 in purified NK and
T cells obtained from IFN-
knockout (-/-) mice were greater than
seen in purified cells from normal controls. In contrast, IL-10
production induced by IL-2 and/or IL-12 was not significantly different
in IFN- (-/-) mice and normal controls. These results suggest
IL-13 expression induced by IL-2 + IL-18 may be regulated by IFN- in
vivo, while IL-10 expression may be IFN--independent. Thus,
depending upon the cell type, IL-18 may act as a strong coinducer of
Th1 or Th2 cytokines. Our findings suggest that IL-12 and IL-18 have
different roles in the regulation of gene expression in NK and T
cells.
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S. Sugawara, A. Uehara, T. Nochi, T. Yamaguchi, H. Ueda, A. Sugiyama, K. Hanzawa, K. Kumagai, H. Okamura, and H. Takada Neutrophil Proteinase 3-Mediated Induction of Bioactive IL-18 Secretion by Human Oral Epithelial Cells J. Immunol., December 1, 2001; 167(11): 6568 - 6575. [Abstract] [Full Text] [PDF]
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 K. Kawakami, Y. Kinjo, S. Yara, K. Uezu, Y. Koguchi, M. Tohyama, M. Azuma, K. Takeda, S. Akira, and A. Saito Enhanced Gamma Interferon Production through Activation of Valpha 14+ Natural Killer T Cells by alpha -Galactosylceramide in Interleukin-18-Deficient Mice with Systemic Cryptococcosis Infect. Immun., November 1, 2001; 69(11): 6643 - 6650. [Abstract] [Full Text] [PDF]
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E. Esfandiari, I. B. McInnes, G. Lindop, F.-P. Huang, M. Field, M. Komai-Koma, X.-q. Wei, and F. Y. Liew A Proinflammatory Role of IL-18 in the Development of Spontaneous Autoimmune Disease J. Immunol., November 1, 2001; 167(9): 5338 - 5347. [Abstract] [Full Text] [PDF]
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S. L. Swain Interleukin 18: Tipping the Balance Towards a T Helper Cell 1 Response J. Exp. Med., August 6, 2001; 194(3): F11 - F14. [Full Text] [PDF]
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R. B. Smeltz, J. Chen, J. Hu-Li, and E. M. Shevach Regulation of Interleukin (IL)-18 Receptor {alpha} Chain Expression on CD4+ T Cells during T Helper (Th)1/Th2 Differentiation: Critical Downregulatory Role of IL-4 J. Exp. Med., July 16, 2001; 194(2): 143 - 154. [Abstract] [Full Text] [PDF]
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T. Hoshino, Y. Kawase, M. Okamoto, K. Yokota, K. Yoshino, K.-i. Yamamura, J.-i. Miyazaki, H. A. Young, and K. Oizumi Cutting Edge: IL-18-Transgenic Mice: In Vivo Evidence of a Broad Role for IL-18 in Modulating Immune Function J. Immunol., June 15, 2001; 166(12): 7014 - 7018. [Abstract] [Full Text] [PDF]
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X. Zhang, J. M. Wang, W. H. Gong, N. Mukaida, and H. A. Young Differential Regulation of Chemokine Gene Expression by 15-Deoxy-{{Delta}}12,1412,14 Prostaglandin J2 J. Immunol., June 15, 2001; 166(12): 7104 - 7111. [Abstract] [Full Text] [PDF]
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D. M. Walter, C. P. Wong, R. H. DeKruyff, G. J. Berry, S. Levy, and D. T. Umetsu IL-18 Gene Transfer by Adenovirus Prevents the Development of and Reverses Established Allergen-Induced Airway Hyperreactivity J. Immunol., May 15, 2001; 166(10): 6392 - 6398. [Abstract] [Full Text] [PDF]
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M. C. Leite-de-Moraes, A. Hameg, M. Pacilio, Y. Koezuka, M. Taniguchi, L. Van Kaer, E. Schneider, M. Dy, and A. Herbelin IL-18 Enhances IL-4 Production by Ligand-Activated NKT Lymphocytes: A Pro-Th2 Effect of IL-18 Exerted Through NKT Cells J. Immunol., January 15, 2001; 166(2): 945 - 951. [Abstract] [Full Text] [PDF]
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 P GARSIDE A role for IL-18 in intestinal inflammation? Gut, January 1, 2001; 48(1): 6 - 7. [Full Text] [PDF]
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 H.-R. Jiang, X.-q. Wei, W. Niedbala, L. Lumsden, F. Y. Liew, and J. V. Forrester IL-18 Not Required for IRBP Peptide-Induced EAU: Studies in Gene-Deficient Mice Invest. Ophthalmol. Vis. Sci., January 1, 2001; 42(1): 177 - 182. [Abstract] [Full Text]
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X.-q. Wei, B. P. Leung, H. M. L. Arthur, I. B. McInnes, and F. Y. Liew Reduced Incidence and Severity of Collagen-Induced Arthritis in Mice Lacking IL-18 J. Immunol., January 1, 2001; 166(1): 517 - 521. [Abstract] [Full Text] [PDF]
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S Chikano, K Sawada, T Shimoyama, S-I Kashiwamura, A Sugihara, K Sekikawa, N Terada, K Nakanishi, and H Okamura IL-18 and IL-12 induce intestinal inflammation and fatty liver in mice in an IFN-gamma dependent manner Gut, December 1, 2000; 47(6): 779 - 786. [Abstract] [Full Text] [PDF]
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 C K Wong, C. Y Ho, E. Li, and C. Lam Elevation of proinflammatory cytokine (IL-18, IL-17, IL-12) and Th2 cytokine (IL-4) concentrations in patients with systemic lupus erythematosus Lupus, October 1, 2000; 9(8): 589 - 593. [Abstract] [PDF]
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Y.-M. Kim, J. Y. Im, S. H. Han, H. S. Kang, and I. Choi IFN-{gamma} Up-Regulates IL-18 Gene Expression Via IFN Consensus Sequence-Binding Protein and Activator Protein-1 Elements in Macrophages J. Immunol., September 15, 2000; 165(6): 3198 - 3205. [Abstract] [Full Text] [PDF]
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A. Mencacci, A. Bacci, E. Cenci, C. Montagnoli, S. Fiorucci, A. Casagrande, R. A. Flavell, F. Bistoni, and L. Romani Interleukin 18 Restores Defective Th1 Immunity to Candida albicans in Caspase 1-Deficient Mice Infect. Immun., September 1, 2000; 68(9): 5126 - 5131. [Abstract] [Full Text] [PDF]
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B. R. Lauwerys, N. Garot, J.-C. Renauld, and F. A. Houssiau Cytokine Production and Killer Activity of NK/T-NK Cells Derived with IL-2, IL-15, or the Combination of IL-12 and IL-18 J. Immunol., August 15, 2000; 165(4): 1847 - 1853. [Abstract] [Full Text] [PDF]
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C.-H. Song, H.-J. Kim, J.-K. Park, J.-H. Lim, U.-O. Kim, J.-S. Kim, T.-H. Paik, K.-J. Kim, J.-W. Suhr, and E.-K. Jo Depressed Interleukin-12 (IL-12), but not IL-18, Production in Response to a 30- or 32-Kilodalton Mycobacterial Antigen in Patients with Active Pulmonary Tuberculosis Infect. Immun., August 1, 2000; 68(8): 4477 - 4484. [Abstract] [Full Text] [PDF]
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J. D. Rempel, M. Wang, and K. T. HayGlass Failure of rIL-12 administration to inhibit established IgE responses in vivo is associated with enhanced IL-4 synthesis by non-B/non-T cells Int. Immunol., July 1, 2000; 12(7): 1025 - 1034. [Abstract] [Full Text] [PDF]
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B. P. Leung, I. B. McInnes, E. Esfandiari, X.-Q. Wei, and F. Y. Liew Combined Effects of IL-12 and IL-18 on the Induction of Collagen-Induced Arthritis J. Immunol., June 15, 2000; 164(12): 6495 - 6502. [Abstract] [Full Text] [PDF]
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J. Urban, H. Fang, Q. Liu, M. J. Ekkens, S.-J. Chen, D. Nguyen, V. Mitro, D. D. Donaldson, C. Byrd, R. Peach, et al. IL-13-Mediated Worm Expulsion Is B7 Independent and IFN-{gamma} Sensitive J. Immunol., April 15, 2000; 164(8): 4250 - 4256. [Abstract] [Full Text] [PDF]
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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]
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 T. Yoshimoto, H. Tsutsui, K. Tominaga, K. Hoshino, H. Okamura, S. Akira, W. E. Paul, and K. Nakanishi IL-18, although antiallergic when administered with IL-12, stimulates IL-4 and histamine release by basophils PNAS, November 23, 1999; 96(24): 13962 - 13966. [Abstract] [Full Text] [PDF]
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