La. Burns et al., GALLIUM ARSENIDE-INDUCED INCREASE IN SERUM CORTICOSTERONE IS NOT RESPONSIBLE FOR SUPPRESSION OF THE IGM ANTIBODY-RESPONSE, The Journal of pharmacology and experimental therapeutics, 268(2), 1994, pp. 740-746
Previous investigations demonstrated gallium arsenide (GaAs) to be an
immunosuppressive agent that alters the function of all cell types inv
olved in the generation of a primary antibody response. In those studi
es, GaAs was administered as a particulate compound that remained in t
he lung at least 14 days after exposure. The extended presence of the
particulate in the lung may induce a stress response that leads to the
release of endogenous corticosteroids. In addition, some of the obser
ved immunomodulatory effects of GaAs were similar to immunological alt
erations reported to be induced by corticosteroids. The present studie
s were designed to determine whether suppression of the immunoglobulin
tig) M antibody-forming calls (AFC) response by GaAs was a result of
a GaAs-induced increase in serum corticosterone. GaAs (50-200 mg/kg) s
ignificantly decreased the weights of both the thymus and spleen and t
he cellularity of the spleen. In addition, there was a GaAs-induced de
crease in the CD4(+)/CD8(+) thymocyte subpopulations and a concomitant
increase in CD4(+) and CD8(+) cells. Within the spleen, there were no
alterations in the percentages of CD4, CD8 or Ig-positive cells. Howe
ver, when expressed as an absolute cell number, there was a 50% decrea
se in the numbers of CD4(+) and CD8(+) cells in the spleen. GaAs also
dose-dependently suppressed (50-75%) the IgM AFC response. The GaAs-in
duced changes in cell populations and immune organ weights were correl
ated with an increase (6- to 10-fold) in serum corticosterone levels.
The treatment of mice with the glucocorticoid antagonist mifepristone
(also called RU 486) blocked the observed alterations in splenic and t
hymic cell populations induced by GaAs. However, mifepristone did not
block the suppression of the AFC response. Neither mifepristone nor ta
ntalum, the particulate control, exerted any immunomodulatory activity
. These studies indicate that GaAs exerts direct effects on splenocyte
s in vivo (suppression of the AFC response) that can be dissociated fr
om the nonspecific effects (alterations in thymus and spleen weight an
d in lymphocyte subpopulations) produced by corticosteroids in respons
e to GaAs exposure.