Putative Pathophysiological Interactions of Cytokines and Phagocytic Cells in

The severe disease and high mortality associated with Plasmodium falciparum infection have traditionally been attributed solely to parasitic virulence factors, but more recent evidence sug-gests that the host's immunologic response may also contribute to the pathophysiology of the disease in humans. This response would be expected to be proportionate-in intensity and na-ture-to the antigenic load created by the sequestration of parasites in the microvasculature and to be directed against the sites of maximal parasitization; thus the immunologic response could potentially contribute to the pathophysiology of both survival and fatal outcome in severe infec-tion. Cytokines appear to playa pivotal role in the activation of the immune response in human falciparum malaria, and their levels correlate with disease severity. The putative mechanisms by which cytokines may mediate both beneficial and deleterious effects by activating phagocytic cells in severe falciparum malaria are discussed. Pathogenesis of Severe Falciparum Malaria After inoculation, malarial sporozoites migrate to the liver, invade hepatocytes, and develop into schizonts, which subsequently release merozoites into the circulation. Mero