Mechanism of iron toxicity.

The subtle balance between proinflammatory and antiinflammatory cytokines plays an important role in determining the severity of the inflammatory reaction and in the anomalous iron handling associated with infection. Conversely, iron deficiency per se appears to limit the severity of the inflammatory response. All of these considerations are at present highly speculative and in need of further experimental and epidemiologic support. If confirmed, the beneficial biological effects of iron depletion may have a defensive role in inflammation and may be perturbed by the nonselective administration of iron to iron-replete patients who would not benefit from such treatment in the first place. In view of the importance of non-transferrin-bound plasma iron (NTBI) in iron toxicity and its rapid cellular uptake, it may play an important role in the harmful effects of iron in infection, and this is illustrated by the infectious complications of parenteral iron therapy in tropical countries.