The past twenty years have seen the appearance of many studies on
the toxicity mechanisms of mineral particles. Silica and asbestos fibres
have often served as models.
The discovery of new mechanistic hypotheses has helped study the effect
of a large number of new molecules, either in prevention or treatment.
Most of these studies have remained at the animal experimentation stage
for the moment. A few clinical tests have however been made.
The mechanisms that have allowed this progress can be summarised as
follows:
1 . Modification of the surface activity of mineral particles by the
covering of their surface or a decrease in their capacity to generate
oxygen radicals.
2. Increase in particular clearance.
3. Decrease in the activation of macrophages and the production of
oxidants.
4. Decrease in the recruitment of inflammatory cells.
5. Decrease in the secretion of inflammation mediators.
6. Decrease in the secretion of growth factors
7. Decrease in collagen synthesis.
8. Decrease in cellular prolifération.
Three main categories of effects can summarise the action of the tested
molecules.
1. Coverine of the surface sites of particies
These are the oldest treatinents. Aluminotherapy and the use of polyvinylpyridine-N-oxide
gave rise to many experimental and clinical studies from 1970 to 1980.
The use of aluminium has been abandoned. PVNO is no longer used in
European countries, which does not appear to, be the case in China.
Amiodarone has been used more recently, but this treatment was soon
abandoned owing to its toxicity.
2. Protection aizainst oxidisiniz stress
Many molecules have been tested for ahnost ten years now: tetrandrine,
ascorbic acid, 21-aminosteroid, superoxide dismutase, catalase, carotene
and vitamin A, cyclic adenosine 3':5'-monophosphate (cAMP).
All these molecules have been tested only experimentally on animals.
3. Inflammatory response and inflammation mediators
Mineral particles activate macrophages which produce cytokines. The
latter recruit polynuclear cells and monocytes.
Growth factors are secreted, inducing the prolifération of fibroblasts
and the synthesis of collagen.
Anti-interleukin-1 antibodies, PNIN anti-rat antisera, anti-bFGFs,
leukocytic anti-integrin antibodies CD 11 a and 11 b and anti-growth
factor antibodies derived from platelets (PDGF) have thus been tested
only experimentally on animals.
These studies are recent and many of them have been published in the
past five years.
These publications as a whole show that a certain number of preventive
or curative treatment leads are under study. The many mechanisms involved
means that it is probably unlikely that a single treatment will be utilisable
but it would be useful if studies were launched in the future on combined
treatments.
The almost complete absence of research on this topic in Western Europe
is to be observed, whereas countries such as China or eastern countries
are highly present.
D. LAFON