Iron and infection: the heart of the matter.

Bacterial resistance to antibiotics is a major threat to clinical medicine. However, natural resistance to bacterial infection, which does not depend on antibiotics, is a powerful protective mechanism common to all mankind. The availability of iron is the heart of the matter and the successful functioning of these antibacterial systems depends entirely upon an extremely low level of free ionic iron (10(-18) M) in normal tissue fluids. This in turn depends on well-oxygenated tissues where the oxidation-reduction potential (Eh) and pH control the binding of iron by unsaturated transferrin and lactoferrin. Bacterial virulence is greatly enhanced by freely available iron, such as that in fully-saturated transferrin or free haemoglobin. Following trauma a fall in tissue Eh and pH due to ischaemia, plus the reducing powers of bacteria, can make iron in transferrin freely available and abolish the bactericidal properties of tissue fluids with disastrous results for the host. Hyperbaric oxygen is a possible therapeutic measure that could restore normal bactericidal systems in infected tissues by raising the Eh and pH.