Occupational Asthma Reference

Palmer K, Coggon D, Does occupational exposure to iron promote infection?, Occup Environ Med, 1997;54:529-534,

Keywords: review, iron, welder, pneumonia, metalworker

Known Authors

David Coggon, Southampton University David Coggon

Keith Palmer, Environmental Epidemiology Unit, Southampton University, UK Keith Palmer

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Abstract

THE BATLE FOR FREE IRON
There is evidence that pathogens adapt in a variety of ways to obtain the iron they
need-for example, by producing their own low molecular weight iron chelators, by modifications to their outer membrane proteins, and by the elaboration of haemolysins which liberate iron from haem." Host organisms counter this by restricting iron availability during infection. Additional iron binding capacity may be recruited in inflammatory exudate, as polymorphonuclear leucocytes degranulate, releasing
lactoferrin;" " while the amount of iron bound to serum transferrin falls (the hypoferraemia of infection) by a mechanism that may entail lactoferrin release, macrophage sequestration of Fe'+-transferrin complexes, and increased synthesis of ferritin. " Dietary iron assimilation is suppressed by as much as 80%; and iron efflux
from macrophages that have digested effete red blood cells is reduced by as much as 70%.6 Other interactions between organism and host may also operate, including the host's immune response to foreign iron sequestering proteins, and the proteolytic cleavage of transferrin and lactoferrin by certain bacteria.' The essential point is that a critical balance exists between commensal or pathogen and host in the fight for available iron. The normal flora of the respiratory tract reflect in part the nutrient
limited balance so achieved. In situations where the balance is disturbed, as for example when exogenous or endogenous supplies of iron exceed the capacity of the iron binding protein system, overgrowth of organisms may be encouraged. Similar considerations may apply in viral infection: although viruses do not require iron,
the host cells they infect need iron before viral replication can occur, and the hypoferraemia of infection has been found in children infected with mumps and chickenpox.

OTHER MECHANISMS OF ACTION
Apart from its role as a nutrient for pathogens, there are other possible ways in which iron could promote infection, especially respiratory tract infection. Iron may be implicated through a mechanism of free radical injury: in vivo iron dependent reduction of hydrogen peroxide generates hydroxyl radicals, the toxic properties of which have recently been reviewed. Studies have shown that metal particles, or carbon coated with metals, can be cytotoxic to macrophages,and short term inhalation experiments in animals have produced a cytotoxic response at ambient concentrations down to 0.1 mg/m.n '9 Factors that interfere with the efficiency of phagocytosis are liable to render the host more susceptible to infection, independent of any effect on the nutrient status
of the pathogen.

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