Endogenous glucocorticoids cause thymus atrophy but are protective during acute Trypanosoma cruzi infection.
The cytokine-mediated stimulation of the hypothalamus-pituitary-adrenal (HPA) axis is relevant for survival during bacterial endotoxemia and certain viral infections. However, only limited information is available regarding the effects of endogenous glucocorticoids on parasite diseases. We have studied this issue using, as a model, C57Bl/6 and Balb/c mice infected with Trypanosoma cruzi, the causal agent of Chagas' disease. These two mouse strains differ in the susceptibility to infection with the parasite. An intense stimulation of the HPA-axis was observed 3 weeks after infection in both strains, but glucocorticoid levels were already increased two- to threefold in the less susceptible Balb/c strain during the first week. Blockade of glucocorticoid receptors with the glucocorticoid antagonist RU486, starting on day 10 after infection, partially reversed the thymic atrophy and decreased the number of CD4(+)CD8(+) thymocytes without affecting parasitemia and the number of inflammatory foci in the heart. However, tumor necrosis factor-alpha blood levels were increased in infected mice of both strains treated with RU486. Furthermore, the blockade of glucocorticoid receptors accelerated death in C57Bl/6J mice and increased lethality to 100% in Balb/c mice. The results obtained represent the first evidence that an endocrine host response that is coupled to the immune process can strongly affect the course of a parasite infection.
Roggero
Eduardo
E
Instituto de Inmunología, Facultad de Ciencias Médicas, Santa Fé 3100, Universidad Nacional de Rosario, 2000 Rosario, Argentina.
Pérez
Ana R
AR
Tamae-Kakazu
Maximiliano
M
Piazzon
Isabel
I
Nepomnaschy
Irene
I
Besedovsky
Hugo O
HO
Bottasso
Oscar A
OA
del Rey
Adriana
A
D000315:Adrenalectomy; D000818:Animals; D000833:Animals, Suckling; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003345:Corticosterone / Q000097:blood; D005434:Flow Cytometry; D005938:Glucocorticoids / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D015735:Mifepristone / Q000494:pharmacology; D009206:Myocardium / Q000473:pathology; D018512:Parasitemia; D011965:Receptors, Glucocorticoid / Q000037:antagonists & inhibitors; D013950:Thymus Gland / Q000473:pathology*; D014349:Trypanosoma cruzi; D014352:Trypanosomiasis / Q000097:blood / Q000276:immunology* / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D005938:Glucocorticoids; D011965:Receptors, Glucocorticoid; D014409:Tumor Necrosis Factor-alpha; D015735:Mifepristone; D003345:Corticosterone