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 Boutlis, C. S.
Right arrow Articles by Anstey, N. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Boutlis, C. S.
Right arrow Articles by Anstey, N. M.

 Previous Article  |  Next Article 

Infection and Immunity, November 2003, p. 6354-6357, Vol. 71, No. 11
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.11.6354-6357.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Plasma Interleukin-12 in Malaria-Tolerant Papua New Guineans: Inverse Correlation with Plasmodium falciparum Parasitemia and Peripheral Blood Mononuclear Cell Nitric Oxide Synthase Activity

Craig S. Boutlis,1,2 Moses Lagog,3 Sujittra Chaisavaneeyakorn,4 Mary A. Misukonis,5 Moses J. Bockarie,3 Charles S. Mgone,6 Zhiqiang Wang,1 Grant Morahan,7 J. Brice Weinberg,5 Venkatachalam Udhayakumar,4 and Nicholas M. Anstey1,8*

International Health Program, Division of Infectious Diseases, Menzies School of Health Research,1 Northern Territory University,2 Flinders University Northern Territory Clinical School, Darwin, Northern Territory,8 Walter and Eliza Hall Institute, Melbourne, Victoria, Australia,7 Papua New Guinea Institute of Medical Research, Madang,3 Papua New Guinea Institute of Medical Research, Goroka, Papua New Guinea,6 Division of Parasitic Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia,4 Division of Hematology-Oncology, Department of Medicine, Veterans Administration and Duke University Medical Centers, Durham, North Carolina5

Received 27 May 2003/ Returned for modification 26 July 2003/ Accepted 2 August 2003

Interleukin-12 (IL-12) has been inversely associated with disease severity in human and murine malaria, and a polymorphism in the IL-12 p40 subunit gene (IL12B) has been associated with susceptibility to human cerebral malaria and reduced nitric oxide (NO) production. To better define the relationships between IL-12, NO, malaria parasitemia, and IL12B polymorphisms during malarial tolerance, plasma IL-12 levels and peripheral blood mononuclear cell NO synthase (NOS) activity were measured in asymptomatic Papua New Guineans exposed to intense malaria transmission. The IL-12 level was strongly inversely correlated with the density of Plasmodium falciparum parasitemia ({rho} = -0.45; P < 0.001) and was predicted to decrease by 19% (95% confidence interval [CI], 10 to 27%) for each twofold increase in P. falciparum parasitemia. This is consistent with a suppressive effect of parasitemia on IL-12 production, an effect previously shown in vitro and in rodent models of disease. The IL-12 level was inversely correlated with NOS activity (r = -0.22; P = 0.007), with each twofold increase in NOS activity being predictive of a 25% (95% CI, 7 to 38%) decrease in plasma IL-12 levels. This probably reflects additional down-regulation of IL-12 by the high basal NO production and monocyte NOS expression found in the malaria-tolerant state. Neither the IL-12 level nor NOS activity was associated with either of two IL12B polymorphisms, reflecting the diversity of genetic control over immune responses in different populations.

* Corresponding author. Mailing address: Menzies School of Health Research, P.O. Box 41096, Casuarina, NT 0811, Australia. Phone: 61 8 8922 8196. Fax: 61 8 8927 5187. E-mail: anstey{at}menzies.edu.au.

Editor: W. A. Petri, Jr.

Infection and Immunity, November 2003, p. 6354-6357, Vol. 71, No. 11
0019-9567/03/$08.00+0     DOI: 10.1128/IAI.71.11.6354-6357.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • MUEHLENBEIN, M. P., ALGER, J., COGSWELL, F., JAMES, M., KROGSTAD, D. (2005). THE REPRODUCTIVE ENDOCRINE RESPONSE TO PLASMODIUM VIVAX INFECTION IN HONDURANS. Am J Trop Med Hyg 73: 178-187 [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»