Antiparasitic effects of tumour necrosis factor in vivo and in vitro

Early experiments in mice suggested that tumour necrosis factor (TNF) might be cytotoxic to asexual blood-stage malaria parasites. This was based on the striking activity of tumour necrosis serum (TNS) on the parasite both in vitro and in vivo, and the inability to separate by physical means the parasite-killing and tumour-killing components. However, recombinant TNF does not have this cytotoxic effect in vitro, while its antiparasitic activity in vivo, though significant, is not as strong as that of an equivalent amount of TNS. Thus it appears that TNS contains another cytotoxic molecule and that TNF itself may act indirectly in vivo, perhaps by activating an effector cell. An example of this has been found in murine schistosomiasis, where macrophage-derived TNF is able to activate eosinophils to attack the infecting worms. One mechanism of schistosomule damage is by eosinophil cationic proteins, and these have also been found to be cytotoxic to blood-stage malaria. There may therefore be a pathway of TNF activity common to both parasites. In a similar way, the crisis-forming factor (CFF) found in the serum of certain immune Sudanese adults is clearly distinct from TNF, since CFF-containing sera do not kill TNF-susceptible tumour cells and rTNF does not kill Plasmodium falciparum in vitro. This confirms that there are other cytotoxic molecules, still to be identified, with a role in immunity to malaria and perhaps other parasites. TNF is also active against intracellular Trypanosoma cruzi and against some viruses but in both cases this appears to be an interferon-like mediatory effect and not direct cytotoxicity. It is not yet clear whether these antiparasitic activities are part of the biological role of TNF.