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Plasma from mice heavily parasitized by Plasmodium vinckei vinckei was found to contain micromolar levels of iron as detected by the 'bleomycin assay' (slightly modified) of Gutteridge et al. [(1981) Biochem. J. 199, 263-265]. Uninfected mouse plasma contained little or no bleomycin-detectable iron. Plasma ultrafiltrate from infected mice contained no bleomycin-detectable iron, indicating that such iron was associated with the protein/macromolecule fraction. We speculate that this iron could catalyse reduction of peroxides in vivo and thus play a role in malaria pathology.

Cerebral malaria in A/J and CBA/H mice infected with Plasmodium berghei ANKA is accompanied by mononuclear cell infiltration, haemorrhage and cerebral endothelial cell damage. This damage is presumably one of the causes of the breakdown of the blood-brain barrier which was detected by measuring the movement of the dye Evans blue and radioisotope labelled albumin and erythrocytes. The density of brain tissue, measured by a Percoll gradient technique, was significantly reduced in mice exhibiting cerebral symptoms, suggesting the occurrence of cerebral oedema.

Because oxygen-centered free radicals are involved in cell-mediated immune responses, we examined the possibility that these reactive species could also have a role in the lymphoproliferative response to alloantigens in the mixed lymphocyte culture (MLC). Three classes of agents that prevent the formation, or damaging effects, of oxygen radicals were tested: the non-permeant electron acceptor ferricyanide; the iron chelators desferrioxamine, desferrithiocin, octanohydroxamic acid, and pyridoxal isonicotinoyl hydrazone, which are thought to be capable of preventing the iron-catalyzed reduction of H2O2 to more reactive species; and the lipid-soluble free radical scavenger butylated hydroxyanisole. These compounds inhibited the proliferation of all potential responder cells in the MLC in a dose-dependent manner. Inhibition was observed only if these agents were present early (less than 40 hr) in the MLC; if added later, their effects were significantly reduced. In contrast, the interleukin 2 (IL 2)-dependent proliferation of CTLL-2 cells or Con A blasts was not affected by these compounds at concentrations that inhibited proliferation in MLC by greater than 90%. Interleukin 1 (IL 1) production by peritoneal exudate cells and IL 2 and IL 1 levels in MLC were not affected by any of the agents tested. By flow microfluorometry, the expression of IL 2 receptors on stimulated T cells was found to be inhibited in the presence of these drugs. Taken together, the data point to an important role for free radical-mediated processes during the early stages of T lymphocyte activation, before IL 2 receptor expression.