Natural resistance, iron and infection: a challenge for clinical medicine, Journal of Medical Microbiology (2006)

Abstract

Natural resistance to infection, which does not depend on antibiotics, is a powerful protective mechanism common to all mankind that has been responsible for the survival of our species during countless millennia in the past. The normal functioning of this complex system of phagocytic cells and tissue fluids is entirely dependent on an extremely low level of free ionic iron (10”18 M) in tissue fluids. This low-iron environment is maintained by the unsaturated iron-binding proteins transferrin and lactoferrin, which depend on well-oxygenated tissues, where a relatively high oxidation–reduction potential (Eh) and pH are essential for the binding of ferric iron. Freely available iron is derived from iron overload, free haem compounds, or hypoxia in injured tissue leading to a fall in Eh and pH. This can severely damage or abolish normal bactericidal mechanisms in tissue fluids leading to overwhelming growth of bacteria or fungi. The challenge for clinical medicine is to reduce or eliminate the presence of freely available iron in clinical disease. In injured or hypoxic tissue, treatment with hyperbaric oxygen might prove very useful by increasing tissue oxygenation and restoring normal bactericidal mechanisms in tissue fluids, which would be of huge benefit to the patient.

"...Conclusions

There is a chain of events in the susceptibility of human tissues to infection that largely or entirely depends upon the availability of freely available iron for the bacteria. Natural resistance to infection operates in an environment where the amount of freely available iron is extremely low. This depends very much on the physical conditions in tissue fluids where the Eh and pH govern the binding of iron to the unsaturated iron-binding proteins transferrin or lactoferrin. The Eh in turn depends on the degree of tissue oxygenation, and therefore hypoxia is of the greatest importance since it produces a fall in tissue Eh, which can result in the production of free ferrous iron and a huge stimulus to bacterial growth. Iron provided by free haem compounds is equally dangerous.

In clinical medicine it might be advantageous to concentrate on those aspects of natural resistance that can be manipulated without the use of antibiotics. This includes a reduction in iron overload during conditions such as acute leukaemia, and in patients undergoing chemotherapy. The use of blood transfusions and blood substitutes based on haemoglobin requires re-examination because these pro- ducts are potentially dangerous. Finally there is the restoration of natural resistance in injured and infected tissues by increased oxygenation. Measurement and control of the Eh and pH would be essential, but it would be of the utmost value if the bactericidal mechanisms in infected tissues could be restored by purely physical means...."

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