THE BIOLOGICAL BASIS OF MALARIAL DISEASE

In this review we summarise the arguments that inflammatory cytokines, triggered by material released from the parasite at schizogony (malar ial toxin), might induce the illness and pathology seen in malaria. Th ese pro-inflammatory cytokines can generate inducible nitric oxide syn thase and cause nitric oxide to be released, as can low concentrations of malarial toxin itself provided interferon-gamma, which has only lo w activity in the absence of malarial toxin, is present. We suggest he re that recently described hypermetabolic functions of these mediators provide a much more plausible explanation for malarial hyperlactataem ia and hypoglycaemia, the chief prognostic indicators in falciparum ma laria, than does hypoxia secondary to mechanical blockage of vessels b y sequestering parasites, which is the dominant current theory. We als o review the arguments that rationalise, through these mediators, the reversibility of the coma of cerebral malaria. Although not Set tested at a cellular level, the proposal that nitric oxide generated in cere bral vascular walls contributes to this coma continues to gather indir ect support. In addition, new evidence incriminating nitric oxide in t he mechanism of tolerance to endotoxin rationalises the raised nitric oxide generation seen in malarial tolerance. (C) 1997 Australian Socie ty for Parasitology. Published by Elsevier Science Ltd.