Immunomodulatory effects of gold sodium thiomalate (gold), which is used as
a therapeutic agent for rheumatoid arthritis, were examined in mice. Ten m
illigrams of gold was intraperitoneally administered once a week and the ad
ministration was continued up to 3 months. The number of lymphocytes yielde
d by the liver, spleen, and thymus decreased during the administration, esp
ecially in the early stage (up to one month). When the administration was c
ontinued up to 3 months, only accelerated thymic atrophy remained. The phen
otypic characterization of lymphocytes after long-term administration (3 mo
nths) revealed that the most prominent change was a decrease in the proport
ion of conventional T cells (CD3(high) IL-2R beta (-)) in various immune or
gans, including the liver and spleen. On the other hand, the proportion of
extrathymic T cells (CD3(int)IL-2R beta (+)) and NKT cells (CD3(int)NK1.1()) tended to increase due to the administration of gold. Other changes incl
uded a decrease in the proportion of granulocytes in all tested organs. The
RT-PCR method confirmed that the relative increase in the sign of V alpha
14 mRNA which is used by NKT cells became prominent as a result of the admi
nistration. Moreover, functional activation of NKT cytotoxicity was induced
at that time. These results suggest that gold mediates the immunomodulatio
n in a different manner depending on lymphocyte subsets.