TNF-inducing malaria toxin: a sheep in wolf's clothing?
It has long been believed that paroxysms of malaria fever are due to a toxin released by rupturing schizonts. The nature of this toxin is beginning to be understood. A critical mediator of malaria fever is tumour necrosis factor (TNF), which is released by monocytes/macrophages and is a potent pyrogen. Rupturing schizonts release a toxin (or toxins) that stimulate macrophages to release TNF. The precise structure of the toxin is unknown but it appears to involve a phosphatidylinositol-like moiety. In addition to causing fever, TNF-inducing toxins are believed to be involved in the pathogenesis of cerebral malaria. However, cerebral malaria occurs in only a small proportion of infected individuals; for the population as a whole, the benefits of the TNF response to the malaria toxin probably outweigh its disadvantages.