Prolonged administration of dexamethasone induces limited reactivation of visceral leishmaniasis in chronically infected BALB/c mice.
Leishmania parasites persist in their vertebrate host after the treatment-induced clinical cure and in the asymptomatic infection. They confer resistance to reinfection but represent a risk of occurrence of acute leishmaniosis in immunosuppressed conditions. We examined the effects of prolonged dexamethasone administration on a chronic Leishmania infantum infection. Splenic T cell populations from the long-term-infected BALB/c mice were reduced by 55%, whereas those from uninfected controls were depleted by 85%. The ability of the remaining spleen cells to produce IL-2, IFN-gamma, IL-4 and TNF-alpha after in vitro specific stimulation decreased twofold, and the specific anti-leishmanial antibodies declined 3- to 5-fold. Liver, spleen and bone marrow are the main L. infantum targets in natural and experimental infections. Three-fold increase of amastigote burden was evidenced in the spleen, after dexamethasone administration was prolonged for over 2 months. No reactivation of Leishmania proliferation was disclosed in the liver and bone marrow. These results show a decreased sensitivity of splenic T cells to dexamethasone in a chronic Leishmania infection and a distinct response of the Leishmania-infected target organs to the dexamethasone-induced immunosuppression.
Rousseau
D
D
Groupe de Recherche en Immunopathologie de la Leishmaniose, Laboratoire de Parasitologie, Faculté de Médecine, avenue de Valombrose, 06107 Nice Cedex 2, France.
Suffia
I
I
Ferrua
B
B
Philip
P
P
Le Fichoux
Y
Y
Kubar
J L
JL
D000818:Animals; D000913:Antibodies, Protozoan / Q000097:blood; D002908:Chronic Disease; D016207:Cytokines / Q000096:biosynthesis; D003907:Dexamethasone / Q000008:administration & dosage*; D005260:Female; D005938:Glucocorticoids / Q000008:administration & dosage*; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D066298:In Vitro Techniques; D018314:Leishmania infantum / Q000276:immunology / Q000302:isolation & purification; D007898:Leishmaniasis, Visceral / Q000209:etiology* / Q000276:immunology / Q000469:parasitology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000276:immunology / Q000469:parasitology; D013601:T-Lymphocytes / Q000276:immunology
D000913:Antibodies, Protozoan; D016207:Cytokines; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D003907:Dexamethasone