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


Boutlis, CS; Lagog, M; Chaisavaneeyakorn, S; Misukonis, MA; Bockarie, MJ; Mgone, CS; Wang, ZQ; Morahan, G; Weinberg, JB; Udhayakumar, V; Anstey, NM
2003-11
INFECTION AND IMMUNITY
Journal Article
71
11
6354-6357
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.
AMER SOC MICROBIOLOGY
CYTOKINE PRODUCTION; IL-12; IMMUNITY; SEVERITY; CHILDREN; SUPPRESSION; MACROPHAGES; MONOCYTES; CHABAUDI; DISEASE
10.1128/IAI.71.11.6354-6357.2003
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Creation Date 2003-11-01 12:00:00