Low plasma arginine concentrations in children with cerebral malaria and decreased nitric oxide production.
Nitric oxide (NO) production and mononuclear cell NO synthase 2 (NOS2) expression are high in healthy Tanzanian children but low in those with cerebral malaria. Factors that downregulate NOS2 also diminish factors involved in cellular uptake and biosynthesis of L-arginine, the substrate for NO synthesis. We therefore postulated that L-arginine concentrations would be low in individuals with cerebral malaria. We measured concentrations of L-arginine in cryopreserved plasma samples from Tanzanian children with and without malaria. L-arginine concentrations were low in individuals with cerebral malaria (mean 46 micromol/L, SD 14), intermediate in those with uncomplicated malaria (70 micromol/L, 20), and within the normal range in healthy controls (122 micromol/L, 22; p<0.0001). Analysis by logistic regression showed that hypoargininaemia was significantly associated with cerebral malaria case-fatality. Hypoargininaemia may contribute to limited NO production in children with cerebral malaria and to severe disease.
Lopansri
Bert K
BK
Division of Infectious Diseases, VA and University of Utah Medical Centers, Salt Lake City, UT, USA.
Anstey
Nicholas M
NM
Weinberg
J Brice
JB
Stoddard
Gregory J
GJ
Hobbs
Maurine R
MR
Levesque
Marc C
MC
Mwaikambo
Esther D
ED
Granger
Donald L
DL
D001120:Arginine / Q000097:blood*; D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D006801:Humans; D016015:Logistic Models; D016779:Malaria, Cerebral / Q000097:blood*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D013636:Tanzania
D009569:Nitric Oxide; D001120:Arginine