Introduction Artemisinin is a sesquiterpene lactone that occurs naturally in the wormweed (Artemisia annua L), an annual plant of wide distribution in the temperate zone between the Balcans and China. Artemisinin was first extracted from the plant, structurally identified and described by Chinese scientists in the early 1970s (1). The compound has strong antimalarial activity directed against asexual and sexual blood forms of all Plasmodium species so far investigated (9). Its blood schizontocidal activity is very rapid, accounting for short fever and parasite clearance times, albeit not exhaustive at the recommended dose regimens and thus fraught with the problem of recrudescence (6). The main indication for the use of artemisinin and its derivatives is the treatment of falciparum malaria, especially in areas with resistance to the common blood schizontocidal compounds.
Iron chelation therapy of Plasmodium falciparum infection alleviates the clinical course of cerebral malaria in children. This study assessed the underlying mechanisms of this therapy. Cytokine stimulation of human (intestinal cell line DLD-1) or murine cells (murine macrophage cell line RAW 264.7) resulted in increased nitric oxide (NO) formation and decreased survival of plasmodia within cocultured human erythrocytes. The addition of desferrioxamine (DFO) before cytokine treatment increased both NO formation and parasite killing but had no effect in the presence of the inhibitor of NO formation, L-N6-(1-iminoethyl)-lysine. Moreover, peroxynitrite, which is formed after chemical reaction of NO with superoxide, appears to be the principal effector molecule for macrophage-mediated cytotoxicity toward P. falciparum, and interferon-gamma is a major regulatory cytokine for this process. The effect of DFO on the clearance of plasmodia appears to be due to enhanced generation of NO, rather than to limitation of iron availability to the parasite.
