PLASMODIUM-FALCIPARUM PRODUCES PROSTAGLANDINS THAT ARE PYROGENIC, SOMNOGENIC, AND IMMUNOSUPPRESSIVE SUBSTANCES IN HUMANS

Plasmodium falciparum causes the most severe form of human malaria, wh ich kills similar to 1.5-2.7 million people every year, but the molecu lar mechanisms underlying the clinical symptoms and the host-parasite interaction remain unclear. We show here that P. falciparum produces p rostaglandins (PGs) D-2, E-2, and F-2 alpha After incubation with 1 mM arachidonic acid (AA), cell homogenates of P. falciparum produced PGs as determined by enzyme immunoassay and gas chromatography-selected i on monitoring. PG production in the parasite homogenate was not affect ed by the nonsteroidal antiinflammatory drugs aspirin and indomethacin , and was partially heat resistant, whereas PG biosynthesis by mammali an cyclooxygenase was completely inhibited by these chemicals and by h eat treatment. Addition of AA to the parasite cell culture markedly in creased an ability of the parasite cell homogenate to produce PGs and of parasitized red blood cells to accumulate PGs in the culture medium . PGD, and PGE, accumulated in the culture medium at the stages of tro phozoites and schizonts more actively than at the ring stage. These fi ndings are the first evidence of the direct involvement of a malaria p arasite in the generation of substances that are pyrogenic and injurio us to the host defenses. We will discuss a possible contribution of th e parasite-produced PGs to pathogenesis and host-parasite interaction of P. falciparum.