Plasma interleukin-12 in malaria-tolerant papua new guineans: inverse correlation with Plasmodium falciparum parasitemia and peripheral blood mononuclear cell nitric oxide synthase activity.
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.
Boutlis
Craig S
CS
International Health Program, Division of Infectious Diseases, Menzies School of Health Research, Northern Territory University, Flinders University Northern Territory Clinical School, Darwin, Australia.
Lagog
Moses
M
Chaisavaneeyakorn
Sujittra
S
Misukonis
Mary A
MA
Bockarie
Moses J
MJ
Mgone
Charles S
CS
Wang
Zhiqiang
Z
Morahan
Grant
G
Weinberg
J Brice
JB
Udhayakumar
Venkatachalam
V
Anstey
Nicholas M
NM
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D018664:Interleukin-12 / Q000097:blood*; D007963:Leukocytes, Mononuclear / Q000201:enzymology*; D016778:Malaria, Falciparum / Q000276:immunology* / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000097:blood*; D010219:Papua New Guinea; D018512:Parasitemia / Q000276:immunology* / Q000378:metabolism
D018664:Interleukin-12; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase