Synergistic effect between ouabain and glucocorticoids for the induction of thymic atrophy.
The present report shows that thymocyte death, induced by glucocorticoids, may be modulated in vivo by ouabain. Young, ten days old, mice injected with 140 mg/kg sodium succcinate of hydrocortisone (HC) intraperitonially (i.p.) displayed, 24 h after the injection, a decrease in thymus size and cellular content, an effect that was magnified when ouabain (OUA) 0.56 mg/kg, i.p. was given 1 h prior to the HC injection. Ouabain per se was not capable of producing these changes. Both HC and the combination OUA plus HC induced the death of immature double positive lymphocytes (CD4+CD8+) whereas CD69+ cells survived both treatments. An increase in annexin positive cells and a decrease in mitochondrial membrane potential, assessed by cytofluorimetry, using the fluorescent dye DiOC6, was observed in thymocytes from HC treated animals indicating apoptosis of these cells. Furthermore, a synergistic effect between OUA and HC was also observed using this parameter. The synergy observed in the thymus of animals treated with glucocorticoids and OUA might occur under stress, when both hormones are released, or in situations when ouabain is administered exogenously in a moment of the circadian cycle when glucocorticoid levels are elevated. However the impact of this effect on the immune response is still unknown.
Rodrigues-Mascarenhas
Sandra
S
Laboratório de Imunologia Tumoral, Instituto de Bioquímica Médica, Centro de Ciências da Saúde, Universidade Federal do Rio de Janeiro, Bloco H - Sala 003, 21941-590, Rio de Janeiro, RJ, Brazil.
dos Santos
Neusa Fernandes
NF
Rumjanek
Vivian M
VM
D000818:Animals; D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D017209:Apoptosis / Q000187:drug effects; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005938:Glucocorticoids / Q000494:pharmacology*; D006854:Hydrocortisone / Q000494:pharmacology; D037181:Lectins, C-Type; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009929:Organ Size / Q000187:drug effects; D010042:Ouabain / Q000494:pharmacology*; D013950:Thymus Gland / Q000166:cytology / Q000187:drug effects* / Q000276:immunology / Q000473:pathology* / Q000502:physiology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D004791:Enzyme Inhibitors; D005938:Glucocorticoids; D006854:Hydrocortisone; D037181:Lectins, C-Type; D010042:Ouabain; D000099192:CD69 Antigens