Gallium arsenide-induced increase in serum corticosterone is not responsible for suppression of the IgM antibody response.
Previous investigations demonstrated gallium arsenide (GaAs) to be an immunosuppressive agent that alters the function of all cell types involved in the generation of a primary antibody response. In those studies, GaAs was administered as a particulate compound that remained in the 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 observed immunomodulatory effects of GaAs were similar to immunological alterations reported to be induced by corticosteroids. The present studies were designed to determine whether suppression of the immunoglobulin (Ig) M antibody-forming calls (AFC) response by GaAs was a result of a GaAs-induced increase in serum corticosterone. GaAs (50-200 mg/kg) significantly decreased the weights of both the thymus and spleen and the cellularity of the spleen. In addition, there was a GaAs-induced decrease 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. However, when expressed as an absolute cell number, there was a 50% decrease in the numbers of CD4+ and CD8+ cells in the spleen. GaAs also dose-dependently suppressed (50-75%) the IgM AFC response. The GaAs-induced changes in cell populations and immune organ weights were correlated 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 thymic cell populations induced by GaAs.(ABSTRACT TRUNCATED AT 250 WORDS)
Burns
L A
LA
Department of Pharmacology and Toxicology, Medical College of Virginia, Virginia Commonwealth University, Richmond.
Spriggs
T L
TL
Fuchs
B A
BA
Munson
A E
AE
D000818:Animals; D001152:Arsenicals / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood*; D016572:Cyclosporine / Q000494:pharmacology; D005260:Female; D005708:Gallium / Q000494:pharmacology*; D007075:Immunoglobulin M / Q000096:biosynthesis*; D016131:Lymphocyte Subsets / Q000187:drug effects; D051379:Mice; D015735:Mifepristone / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects
D001152:Arsenicals; D007075:Immunoglobulin M; C043055:gallium arsenide; D015735:Mifepristone; D016572:Cyclosporine; D005708:Gallium; D003345:Corticosterone