Anti-lactoferrin toxicity and elevated iron: The environmental prerequisites which activate susceptibility to tuberculosis infection?

Med Hypotheses. 2006;66(3):513-7. doi: 10.1016/j.mehy.2005.09.027. Epub 2005 Dec 1.

Abstract

The maintenance and multiplication of Mycobacteria tuberculosis (TB) and many other species of parasitic pathogen are dependent to varying, largely unidentified degrees upon a source of free iron within the host tissues. To combat these infections, the mammalian biosystem expresses an iron binding exocrine protein, lactoferrin, which scavenges and competes for free iron, thereby starving the parasite of its vital iron supply. TB mycobacteria are naturally endemic in the external environment, and once a latent, low level TB infection is established within the host tissues, a full blown proliferation of the mycobacteria population can be activated as soon as the levels of free iron are elevated within the host tissues. The increase in iron can be induced by several environmental and/or eco-genetic prerequisites that operate either singly or in a synergistic combination; factors such as iron rich water/foods, increased iron uptake/retention in the host tissues or an environmental/genetic induced reduction in the turn over of iron binding lactoferrin mediated immune defence against TB. Susceptibility to the full blown proliferation of TB pathogenesis is markedly increased as a result. This paper proposes that the recent dramatic increase in the incidence of bovine/badger TB across the UK can be correlated to the overall increase in acidification of the agricultural ecosystem, which, in turn, has induced a substantial elevation of soluble iron within the farm foodchain, thereby exacerbating susceptibility to TB infection within any mammalian species that is dependent upon these high iron ecosystems. The problem is further compounded by the routine use of 'anti-lactoferrin' levamisole based cattle wormers, which 'sensitise' the levamisole's target receptors, thereby down regulating the secretion of the iron binding lactoferrin molecule, which causes a reduction in the host's main line of defence against TB infection.

MeSH terms

  • Animals
  • Cattle
  • Disease Susceptibility
  • Down-Regulation
  • Environment
  • Iron / metabolism*
  • Lactoferrin / chemistry*
  • Levamisole / pharmacology
  • Mustelidae
  • Mycobacterium tuberculosis / metabolism*
  • Mycobacterium tuberculosis / pathogenicity
  • Protein Binding
  • Receptors, Cell Surface / biosynthesis
  • Tuberculosis / etiology*
  • Tuberculosis / prevention & control

Substances

  • Receptors, Cell Surface
  • lactoferrin receptors
  • Levamisole
  • Iron
  • Lactoferrin