Plasma Interleukin-12 in malaria-tolerant Papua New Guineans : inverse correlation with Plasmodium falciparum parasitemia and peripheral blood mononuclear cell nitric oxide synthase activity

C.S. Boutlis, M. Lagog, S. Chaisavaneeyakorn, M.A. Misukonis, M.J. Bockarie, C.S. Mgone, Z. Wang, Grant Morahan, J.B. Weinberg, V. Udhayakumar, N.M. Anstey

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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 (ρ = −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.
Original languageEnglish
Pages (from-to)6354-6357
JournalInfection and Immunity
Volume71
Issue number11
DOIs
Publication statusPublished - 2003

Fingerprint Dive into the research topics of 'Plasma Interleukin-12 in malaria-tolerant Papua New Guineans : inverse correlation with Plasmodium falciparum parasitemia and peripheral blood mononuclear cell nitric oxide synthase activity'. Together they form a unique fingerprint.

Cite this