revised final - Agency for Toxic Substances and Disease Registry ...

MERCURY 274
2. HEALTH EFFECTS
1992; Goh and Ng 1988; Pambor and Timmel 1989; Skoglund and Egelrud 1991; Veien 1990). Additionally,
mercury may cause either decreases in immune activity or an autoimmune response, depending on the genetic
predisposition of the individual exposed. The human data are very limited, and only decreased IgG
production has been observed in workers chronically exposed to metallic mercury vapor at chloralkali and ore
production plants (Bencko et al. 1990; Moszczynski et al. 1990b). Neither of these studies, however, adjusted
for smoking or alcohol. Increases in serum immunoglobulins (IgA, IgG, IgE, or IgM) and autoantibody titres
(antilaminin or antiglomerular basement membrane antibodies) have not been observed in similarly exposed
populations (Bernard et al. 1987; Cardenas et al. 1993; Langworth et al. 1992b). There is limited information
in humans that suggests that certain individuals may develop an autoimmune response when exposed to
mercury. Deposition of IgG and complement C3 have been observed in the glomeruli of two workers with
mercury-induced proteinuria (Tubbs et al. 1982). Also, increased antiglomerular basement membrane
antibodies and elevated antinuclear antibodies have been observed in a few persons with exposure to mercury
in dental amalgams (Anneroth et al. 1992). After removal of one dental amalgam, a significant decrease in
IgE levels was observed. Within the populations described above that showed no overall increase in immune
parameters, individuals in these groups showed either increases in anti-DNA antibody titres or antiglomerular
basement membrane responses (Cardenas et al. 1993; Langworth et al. 1992b). Moszczynski et al. (1995)
studied workers exposed to mercury vapor and reported a positive correlation between the T-helper cell count
and the duration of exposure. The combined stimulation of the T-cell line and an observed decrease in the
helper/suppressor ratio were suggestive of an autoimmune response.
The immune system reaction to mercury has been extensively studied in animals. Although it has not
been completely described, a great deal of information exists about the changes that occur in the immune
system in response to mercury exposure (Bigazzi 1992; Goldman et al. 1991; Mathieson 1992).
Animal strains that are susceptible or predisposed to develop an autoimmune response show a
proliferation of autoreactive T-cells (specifically CD4+ T-cells) (Pelletier et al. 1986; Rossert et al. 1988).
The fundamental change caused by mercury that results in the autoimmune response appears to be in these
autoreactive T-cells, since transfer of these cells to an unexposed animal results in the development of the
autoimmune response in the unexposed animal (Pelletier et al. 1988). A subset of the CD4+ T-cells, the Th2
cells, are activated and induce polyclonal B-cell activation (possibly through the release of interleukin-4
[IL-4]), which results in IgE production by the B-cells (Ochel et al. 1991). The increases in serum IgE are
paralleled by increases in MHC molecule expression on the B-cells (Dubey et al. 1991a). These changes are
accompanied by enlargement of the spleen and lymph nodes, an increase in the number of spleen cells