This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ohkusu, K.
Right arrow Articles by Nakanishi, K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ohkusu, K.
Right arrow Articles by Nakanishi, K.

 Previous Article  |  Next Article 

Infection and Immunity, May 2000, p. 2449-2456, Vol. 68, No. 5
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Potentiality of Interleukin-18 as a Useful Reagent for Treatment and Prevention of Leishmania major Infection

Kazunobu Ohkusu,1 Tomohiro Yoshimoto,1,2,3 Kiyoshi Takeda,3,4 Takeharu Ogura,1 Shin-ichiro Kashiwamura,2 Yoichiro Iwakura,5 Shizuo Akira,3,4 Haruki Okamura,2,3 and Kenji Nakanishi1,2,3,*

Department of Immunology and Medical Zoology1 and Laboratory of Host Defenses, Institute for Advanced Medical Sciences,2 Hyogo College of Medicine, Nishinomiya, Hyogo 663-8501, Department of Host Defenses, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871,4 Laboratory Animal Research Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639,5 and Core Research for Evolutional Science and Technology, Japan Science and Technology Corporation, Tokyo,3 Japan

Received 3 November 1999/Returned for modification 5 December 1999/Accepted 26 January 2000

Interleukin-18 (IL-18) is a proinflammatory cytokine that plays an important role in natural killer cell activation and the T helper 1 (Th1) cell response, particularly in collaboration with IL-12. Since Th1 cells play a pivotal role in the host defense against infection with intracellular microbes, such as Leishmania major, we investigated whether IL-18 is critically involved in protection against L. major infection by activation of Th1 cells. We administered IL-12 and/or IL-18 daily to L. major-susceptible BALB/c mice. Neither IL-12 (10 ng/mouse) nor IL-18 (1,000 ng/mouse) induced wound healing, while daily injection of IL-12 and IL-18 during the first week after infection strongly protected the mice from footpad swelling by induction and activation of Th1 cells. Furthermore, these mice acquired protective immunity. We also investigated a protective role of endogenous IL-18 by using anti-IL-18 antibody-treated C3H/HeN mice (an L. major-resistant strain) or IL-18 deficient (IL-18-/-) mice with a resistant background (C57BL/6). We found that in the absence of endogenous IL-18, these mice showed prolonged footpad swelling as well as diminished nitric oxide production. However, daily injection of IL-18 into IL-18-/- mice corrected their deficiencies, suggesting that these mice have Th1 cells that produce gamma interferon (IFN-gamma ) in response to IL-18. Indeed, these mice had normal levels of Th1 cells. Thus, IL-18 is not responsible for inducing Th1 cells but participates in host resistance by its action in stimulating Th1 cells to produce IFN-gamma . Our results also indicate the high potentiality of IL-18 as a useful reagent for treatment as well as prevention against reinfection.

* Corresponding author. Mailing address: Department of Immunology and Medical Zoology, Hyogo College of Medicine, 1-1, Mukogawa-cho, Nishinomiya, Hyogo 663-8501 Japan. Phone: 81-(798) 45-6573. Fax: 81-(798) 40-5423. E-mail: nakaken{at}hyo-med.ac.jp.

Infection and Immunity, May 2000, p. 2449-2456, Vol. 68, No. 5
0019-9567/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Doi, T., Sakoda, T., Akagami, T., Naka, T., Mori, Y., Tsujino, T., Masuyama, T., Ohyanagi, M. (2008). Aldosterone induces interleukin-18 through endothelin-1, angiotensin II, Rho/Rho-kinase, and PPARs in cardiomyocytes. Am. J. Physiol. Heart Circ. Physiol. 295: H1279-H1287 [Abstract] [Full Text]  
  • Yoshimoto, T., Yoshimoto, T., Yasuda, K., Mizuguchi, J., Nakanishi, K. (2007). IL-27 Suppresses Th2 Cell Development and Th2 Cytokines Production from Polarized Th2 Cells: A Novel Therapeutic Way for Th2-Mediated Allergic Inflammation. J. Immunol. 179: 4415-4423 [Abstract] [Full Text]  
  • Rowland, C. A., Lertmemongkolchai, G., Bancroft, A., Haque, A., Lever, M. S., Griffin, K. F., Jackson, M. C., Nelson, M., O'Garra, A., Grencis, R., Bancroft, G. J., Lukaszewski, R. A. (2006). Critical Role of Type 1 Cytokines in Controlling Initial Infection with Burkholderia mallei. Infect. Immun. 74: 5333-5340 [Abstract] [Full Text]  
  • Sasaki, Y., Yoshimoto, T., Maruyama, H., Tegoshi, T., Ohta, N., Arizono, N., Nakanishi, K. (2005). IL-18 with IL-2 protects against Strongyloides venezuelensis infection by activating mucosal mast cell-dependent type 2 innate immunity. JEM 202: 607-616 [Abstract] [Full Text]  
  • Fernandez-Lago, L., Orduna, A., Vizcaino, N. (2005). Reduced interleukin-18 secretion in Brucella abortus 2308-infected murine peritoneal macrophages and in spleen cells obtained from B. abortus 2308-infected mice. J Med Microbiol 54: 527-531 [Abstract] [Full Text]  
  • Akhiani, A. A., Schon, K., Lycke, N. (2004). Vaccine-Induced Immunity against Helicobacter pylori Infection Is Impaired in IL-18-Deficient Mice. J. Immunol. 173: 3348-3356 [Abstract] [Full Text]  
  • Dumas, C., Muyombwe, A., Roy, G., Matte, C., Ouellette, M., Olivier, M., Papadopoulou, B. (2003). Recombinant Leishmania major Secreting Biologically Active Granulocyte-Macrophage Colony-Stimulating Factor Survives Poorly in Macrophages In Vitro and Delays Disease Development in Mice. Infect. Immun. 71: 6499-6509 [Abstract] [Full Text]  
  • von Stebut, E., Ehrchen, J. M., Belkaid, Y., Kostka, S. L., Molle, K., Knop, J., Sunderkotter, C., Udey, M. C. (2003). Interleukin 1{alpha} Promotes Th1 Differentiation and Inhibits Disease Progression in Leishmania major-susceptible BALB/c Mice. JEM 198: 191-199 [Abstract] [Full Text]  
  • Reddy, P., Teshima, T., Hildebrandt, G., Williams, D. L., Liu, C., Cooke, K. R., Ferrara, J. L.M. (2003). Pretreatment of donors with interleukin-18 attenuates acute graft-versus-host disease via STAT6 and preserves graft-versus-leukemia effects. Blood 101: 2877-2885 [Abstract] [Full Text]  
  • Zhu, M., Xu, X., Liu, H., Liu, X., Wang, S., Dong, F., Yang, B., Song, G. (2003). Enhancement of DNA vaccine potency against herpes simplex virus 1 by co-administration of an interleukin-18 expression plasmid as a genetic adjuvant. J Med Microbiol 52: 223-228 [Abstract] [Full Text]  
  • Gracie, J. A., Robertson, S. E., McInnes, I. B. (2003). Interleukin-18. J. Leukoc. Biol. 73: 213-224 [Abstract] [Full Text]  
  • Aguilar Torrentera, F., Laman, J. D., Van Meurs, M., Adorini, L., Muraille, E., Carlier, Y. (2002). Endogenous Interleukin-12 Is Critical for Controlling the Late but Not the Early Stage of Leishmania mexicana Infection in C57BL/6 Mice. Infect. Immun. 70: 5075-5080 [Abstract] [Full Text]  
  • Kinjo, Y., Kawakami, K., Uezu, K., Yara, S., Miyagi, K., Koguchi, Y., Hoshino, T., Okamoto, M., Kawase, Y., Yokota, K., Yoshino, K., Takeda, K., Akira, S., Saito, A. (2002). Contribution of IL-18 to Th1 Response and Host Defense Against Infection by Mycobacterium tuberculosis: A Comparative Study with IL-12p40. J. Immunol. 169: 323-329 [Abstract] [Full Text]  
  • Stuyt, R. J. L., Netea, M. G., Verschueren, I., Fantuzzi, G., Dinarello, C. A., Van der Meer, J. W. M., Kullberg, B. J. (2002). Role of Interleukin-18 in Host Defense against Disseminated Candida albicans Infection. Infect. Immun. 70: 3284-3286 [Abstract] [Full Text]  
  • Singh, R. P., Kashiwamura, S.-i., Rao, P., Okamura, H., Mukherjee, A., Chauhan, V. S. (2002). The Role of IL-18 in Blood-Stage Immunity Against Murine Malaria Plasmodium yoelii265 and Plasmodium bergheiANKA. J. Immunol. 168: 4674-4681 [Abstract] [Full Text]  
  • Kawakami, K., Kinjo, Y., Yara, S., Uezu, K., Koguchi, Y., Tohyama, M., Azuma, M., Takeda, K., Akira, S., Saito, A. (2001). 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. 69: 6643-6650 [Abstract] [Full Text]  
  • Helmby, H., Takeda, K., Akira, S., Grencis, R. K. (2001). Interleukin (Il)-18 Promotes the Development of Chronic Gastrointestinal Helminth Infection by Downregulating IL-13. JEM 194: 355-364 [Abstract] [Full Text]  
  • Murray, H. W. (2001). Clinical and Experimental Advances in Treatment of Visceral Leishmaniasis. Antimicrob. Agents Chemother. 45: 2185-2197 [Full Text]  
  • Harandi, A. M., Svennerholm, B., Holmgren, J., Eriksson, K. (2001). Interleukin-12 (IL-12) and IL-18 Are Important in Innate Defense against Genital Herpes Simplex Virus Type 2 Infection in Mice but Are Not Required for the Development of Acquired Gamma Interferon-Mediated Protective Immunity. J. Virol. 75: 6705-6709 [Abstract] [Full Text]  
  • Cai, G., Kastelein, R., Hunter, C. A. (2000). Interleukin-18 (IL-18) Enhances Innate IL-12-Mediated Resistance to Toxoplasma gondii. Infect. Immun. 68: 6932-6938 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»