J Med Microbiol International Journal of Systematic and Evolutionary Microbiology
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J Med Microbiol 55 (2006), 251-258; DOI: 10.1099/jmm.0.46386-0
© 2006 Society for General Microbiology
ISSN 0022-2615

Review

Natural resistance, iron and infection: a challenge for clinical medicine

John J. Bullen1,2, Henry J. Rogers1, Paul B. Spalding2 and C. Gillon Ward1,2

1 National Institute for Medical Research, Mill Hill, London NW7 1AA, UK

2 Department of Surgery, School of Medicine, University of Miami, PO Box 016310, Miami, FL 33101, USA

Correspondence
John Bullen
john.bullen{at}tiscali.fr


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.




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