Opposed circulating plasma levels of endothelin-1 and C-type natriuretic peptide in children with Plasmodium falciparum malaria.
BACKGROUND
Molecular mechanisms involved in the pathogenesis of severe Plasmodium falciparum malaria (SM), are not yet fully understood. Both endothelin-1 (ET-1) and C-type natriuretic peptide (CNP) are produced by vascular endothelium and act locally as paracrine regulators of vascular tone, ET-1 being a potent vasoconstrictor and CNP having strong vasorelaxant properties.


METHODS
Plasma levels of ET-1 and N-terminal fragments of CNP (NT-proCNP) were studied on admission and after 24 hours of treatment, using enzyme-linked-immunosorbent-assay (ELISA) technique, in Gabonese children with severe falciparum malaria (SM, n = 50), with uncomplicated malaria (UM, n = 39) and healthy controls (HC, n = 25).


RESULTS
Compared to HC, malaria patients had significantly higher plasma levels of ET-1 and significantly lower levels of NT-proCNP (p < 0.001 and p < 0.024 respectively). Plasma levels of NT-proCNP were additionally decreased in SM patients compared to HC (p = 0.034), whereas UM was not significantly different to HC. In the SM group we found a trend towards lower ET-1 levels compared to UM (p = 0.085).


CONCLUSIONS
In the present study, an imbalance between the vasoconstricitve and vasorelaxant endothelium-derived substances ET-1 and CNP in the plasma of children with falciparum malaria is demonstrated, presumably in favor of vasoconstrictive and pro-inflammatory effects. These results may indicate involvement of ET-1 and CNP in malaria pathogenesis. Furthermore, results of lower ET-1 and CNP levels in SM may reflect endothelial cell damage.
Dietmann
Anelia
A
Clinical Department of Neurology, Innsbruck Medical University, Innsbruck, Austria. Anelia.Dietmann@i-med.ac.at
Lackner
Peter
P
Helbok
Raimund
R
Spora
Katharina
K
Issifou
Saadou
S
Lell
Bertrand
B
Reindl
Markus
M
Kremsner
Peter G
PG
Schmutzhard
Erich
E
D000704:Analysis of Variance; D000818:Animals; D000962:Antimalarials / Q000627:therapeutic use; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004338:Drug Combinations; D019332:Endothelin-1 / Q000097:blood*; D004730:Endothelium, Vascular / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005681:Gabon / Q000453:epidemiology; D006801:Humans; D007223:Infant; D016778:Malaria, Falciparum / Q000097:blood / Q000188:drug therapy / Q000276:immunology* / Q000469:parasitology; D008297:Male; D020098:Natriuretic Peptide, C-Type / Q000097:blood*; D010963:Plasmodium falciparum / Q000276:immunology*; D011739:Pyrimethamine / Q000627:therapeutic use; D011803:Quinine / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D013413:Sulfadoxine / Q000627:therapeutic use
D000962:Antimalarials; D004338:Drug Combinations; D019332:Endothelin-1; D020098:Natriuretic Peptide, C-Type; C001205:fanasil, pyrimethamine drug combination; D013413:Sulfadoxine; D011803:Quinine; D011739:Pyrimethamine