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 Mohan, K.
Right arrow Articles by Stevenson, M. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mohan, K.
Right arrow Articles by Stevenson, M. M.

 Previous Article  |  Next Article 

Infection and Immunity, February 1999, p. 513-519, Vol. 67, No. 2
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Therapy with a Combination of Low Doses of Interleukin 12 and Chloroquine Completely Cures Blood-Stage Malaria, Prevents Severe Anemia, and Induces Immunity to Reinfection

Karkada Mohan, Hakeem Sam, and Mary M. Stevenson*

Centre for the Study of Host Resistance, McGill University, and The Montreal General Hospital Research Institute, Montreal, Quebec H3G 1A4, Canada

Received 13 August 1998/Returned for modification 14 October 1998/Accepted 11 November 1998

The immunoregulatory cytokine interleukin 12 (IL-12) induces host resistance against experimental malaria. In this study, we tested the feasibility of using IL-12 in combination with chloroquine (CQ) to rescue susceptible A/J mice from lethal blood-stage Plasmodium chabaudi AS infection. Combined treatment with low doses of CQ and IL-12 resulted in a >15-fold reduction in the parasite load and 100% survival of A/J mice with established infections. Compared to control mice, which succumbed to severe anemia, CQ-plus-IL-12-treated mice had significantly higher early- and late-stage erythroid-cell progenitors in the bone marrow and spleen, resulting in significantly higher hematocrits, erythrocyte counts, and percentages of reticulocytes. Production of parasite-specific gamma interferon (IFN-gamma ) by splenocytes from these mice was upregulated >20-fold relative to controls in parallel with enhanced IFN-gamma mRNA expression. Further, enhanced responsiveness to IL-12 and increased downstream IFN-gamma production in CQ-plus-IL-12-treated mice was evident from increased mRNA expression for the beta 1 and beta 2 subunits of IL-12 receptor in the splenocytes. Moreover, this combined therapy induced higher levels of anti-malaria antibodies than did CQ alone as well as sterile immunity against reinfection. Because IL-12 can be used at low doses and is effective even in established infections, it may be feasible to use this immunochemotherapeutic approach in human malaria.

* Corresponding author. Mailing address: Montreal General Hospital Research Institute 1650 Cedar Ave., Montreal, Quebec H3G 1A4, Canada. Phone: (514) 937-6011 ext. 4507. Fax: (514) 934-8332. E-mail: mcev{at}musica.mcgill.ca.

Infection and Immunity, February 1999, p. 513-519, Vol. 67, No. 2
0019-9567/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Metenou, S., Dembele, B., Konate, S., Dolo, H., Coulibaly, S. Y., Coulibaly, Y. I., Diallo, A. A., Soumaoro, L., Coulibaly, M. E., Sanogo, D., Doumbia, S. S., Wagner, M., Traore, S. F., Klion, A., Mahanty, S., Nutman, T. B. (2009). Patent Filarial Infection Modulates Malaria-Specific Type 1 Cytokine Responses in an IL-10-Dependent Manner in a Filaria/Malaria-Coinfected Population. J. Immunol. 183: 916-924 [Abstract] [Full Text]  
  • DJIMDE, A. A., DOUMBO, O. K., TRAORE, O., GUINDO, A. B., KAYENTAO, K., DIOURTE, Y., NIARE-DOUMBO, S., COULIBALY, D., KONE, A. K., CISSOKO, Y., TEKETE, M., FOFANA, B., DICKO, A., DIALLO, D. A., WELLEMS, T. E., KWIATKOWSKI, D., PLOWE, C. V. (2003). CLEARANCE OF DRUG-RESISTANT PARASITES AS A MODEL FOR PROTECTIVE IMMUNITY IN PLASMODIUM FALCIPARUM MALARIA. Am J Trop Med Hyg 69: 558-563 [Abstract] [Full Text]  
  • Chaisavaneeyakorn, S., Othoro, C., Shi, Y. P., Otieno, J., Chaiyaroj, S. C., Lal, A. A., Udhayakumar, V. (2003). Relationship between Plasma Interleukin-12 (IL-12) and IL-18 Levels and Severe Malarial Anemia in an Area of Holoendemicity in Western Kenya. CVI 10: 362-366 [Abstract] [Full Text]  
  • Angulo, I., Fresno, M. (2002). Cytokines in the Pathogenesis of and Protection against Malaria. CVI 9: 1145-1152 [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]  
  • Cravo, P., Culleton, R., Hunt, P., Walliker, D., Mackinnon, M. J. (2001). Antimalarial Drugs Clear Resistant Parasites from Partially Immune Hosts. Antimicrob. Agents Chemother. 45: 2897-2901 [Abstract] [Full Text]  
  • Greenberg, P. L., Gordeuk, V., Issaragrisil, S., Siritanaratkul, N., Fucharoen, S., Ribeiro, R. C. (2001). Major Hematologic Diseases in the Developing World-- New Aspects of Diagnosis and Management of Thalassemia, Malarial Anemia, and Acute Leukemia. ASH Education Book 2001: 479-498 [Abstract] [Full Text]  
  • Choudhury, H. R., Sheikh, N. A., Bancroft, G. J., Katz, D. R., de Souza, J. B. (2000). Early Nonspecific Immune Responses and Immunity to Blood-Stage Nonlethal Plasmodium yoelii Malaria. Infect. Immun. 68: 6127-6132 [Abstract] [Full Text]  
  • Luty, A. J. F., Perkins, D. J., Lell, B., Schmidt-Ott, R., Lehman, L. G., Luckner, D., Greve, B., Matousek, P., Herbich, K., Schmid, D., Weinberg, J. B., Kremsner, P. G. (2000). Low Interleukin-12 Activity in Severe Plasmodium falciparum Malaria. Infect. Immun. 68: 3909-3915 [Abstract] [Full Text]  
  • Martiney, J. A., Sherry, B., Metz, C. N., Espinoza, M., Ferrer, A. S., Calandra, T., Broxmeyer, H. E., Bucala, R. (2000). Macrophage Migration Inhibitory Factor Release by Macrophages after Ingestion of Plasmodium chabaudi-Infected Erythrocytes: Possible Role in the Pathogenesis of Malarial Anemia. Infect. Immun. 68: 2259-2267 [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»