Chemistry Reference
In-Depth Information
10.3 Acceleration of Spontaneous
Autoimmune Diseases by
Cadmium and Lead
Recent studies using Cd and Pb have expanded the
results obtained by Hg. Cd in a high dose increased
the ANA in autoimmune-prone NZBWF1 mice during
the fi rst months of treatment, whereas a lower dose
increased the IgG2a serum level and the proteinuria,
although without affecting the IC deposition (Leffel
et
al.,
2003). As mentioned previously, Pb enhances the
autoimmune manifestations in autoimmune-prone
NZBWF1 hybrid mice (Rudofsky and Lawrence, 1999).
A recent study on lead in four New Zealand mixed
strains revealed a complex relation between the spon-
taneous autoimmune disease, Pb exposure, genetics,
and gender, leading to different phenotypic outcome:
both acceleration and inhibition of the autoimmune
condition were observed (Hudson
et al.,
2003).
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10.4 Comments on the Autoimmune
Effects of Metals
The ability of metals to accelerate and aggravate
genetically, as well as nongenetically, determined
autoimmune disease processes in rodents is an
important new observation in the immunotoxicology
of metals. Although a few of these studies included
some dose-response data, the potential importance of
these fi ndings for human conditions and the variation
in phenotypic expression of the effect of metals war-
rant further dose-response studies in all autoimmune
models. In addition, the mechanism(s) by which the
metals are able to accelerate the autoimmune proc-
ess should be examined, which will also improve
the understanding of the general mechanisms in
autoimmune diseases.
Therefore, new fi ndings in rodents such as major
genetic factors regulating susceptibility to induction
of autoimmunity by mercury, silver, and gold; the
existence of genetic factors determining uptake and
retention of metals, as well as the threshold of metals
for elicitation of autoimmunity; and the accelerating/
aggravating effect of metals such as mercury, cad-
mium, and lead on spontaneous autoimmune condi-
tions are all reasons why metals may be of importance
for autoimmune conditions in humans. Although case
reports in humans are evidence for the ability of metals
like mercury and gold to induce autoimmune condi-
tions, determining the importance of metal exposure
for human autoimmune disease will require further
studies.
