In interferon-γ activated human macrophages, GTP-cyclohydrolase 1 catalyses the conversion of guanosine triphosphate to 7,8-dihydroneopterin triphosphate, which is dephosphorylated and oxidized to form neopterin. Elevated levels of neopterin have been detected in the urine and serum of malaria-infected patients. In this study, U937 cells were treated with interferon-γ and one of the following antimalarial drugs: amodiaquine, artemisinin, chloroquine, doxycycline, primaquine, pyrimethamine or quinine. The effects of treating the U937 cells with malaria pigment (β-haematin), latex beads, or Plasmodium falciparum-infected-red blood cell lysates were also investigated. U937 GTP-cyclohydrolase 1 mRNA expression was monitored using reverse-transcriptase-quantitative PCR. Artemisinin, primaquine, and quinine down-regulated GTP-cyclohydrolase 1 gene expression 1.26-, 1.29-, and 1.63-fold, respectively. The remaining drugs had insignificant effects. β-haematin up-regulated GTP-cyclohydrolase 1 mRNA expression 1.18-fold, whereas P. falciparum-infected red blood cell lysate down-regulated expression 1.56-fold. These results show the differing immunomodulatory actions of antimalarial drugs and malaria pigment taking place in monocytes.
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