PLASMODIUM-FALCIPARUM PIGMENT INDUCES MONOCYTES TO RELEASE HIGH-LEVELS OF TUMOR-NECROSIS-FACTOR-ALPHA AND INTERLEUKIN-1-BETA

We show that high levels of tumor necrosis factor-alpha (TNF-alpha) ac tivity were consistently detected when monocytes were cocultured with Plasmodium falciparum schizont stage-parasitized erythrocytes that sub sequently ruptured. Isolated pigment recovered from ruptured schizonts was found to specifically induce monocyte release of high levels of T NF-alpha and interleukin-1 beta (IL-1 beta). Particulate free-culture supernatant that contained various soluble parasite macromolecules ind uced relatively low levels of TNF-alpha and IL-1 beta. When isolated p igment was treated with protease, the monokine inducing-activity was a bolished. Isolated pigment prepared from different natural isolates of P. falciparum stimulated variable levels of monokine production. We p ropose that in vivo, malaria pigment from parasites sequestered in the host microvasculature is a physiologically relevant moiety that inter acts with monocytes and stimulates the release of TNF-alpha and IL-1 b eta. These observations suggest that malaria pigment may be a virulenc e factor in the monokine-mediated induction of organ-specific and syst emic pathophysiology in falciparum malaria.