Adrenal hormones mediate disease tolerance in malaria.

Malaria reduces host fitness and survival by pathogen-mediated damage and inflammation. Disease tolerance mechanisms counter these negative effects without decreasing pathogen load. Here, we demonstrate that in four different mouse models of malaria, adrenal hormones confer disease tolerance and protect against early death, independently of parasitemia. Surprisingly, adrenalectomy differentially affects malaria-induced inflammation by increasing circulating cytokines and inflammation in the brain but not in the liver or lung. Furthermore, without affecting the transcription of hepatic gluconeogenic enzymes, adrenalectomy causes exhaustion of hepatic glycogen and insulin-independent lethal hypoglycemia upon infection. This hypoglycemia is not prevented by glucose administration or TNF-α neutralization. In contrast, treatment with a synthetic glucocorticoid (dexamethasone) prevents the hypoglycemia, lowers cerebral cytokine expression and increases survival rates. Overall, we conclude that in malaria, adrenal hormones do not protect against lung and liver inflammation. Instead, they prevent excessive systemic and brain inflammation and severe hypoglycemia, thereby contributing to tolerance.

Endocrine, metabolic, and immunologic components of HIV infection.

It is generally accepted that the progression of HIV infection is the consequence of increased HIV virus load and defective CD4(+) T cell-mediated immunity. Previous studies have shown that T helper-directed cellular immunity is suppressed in hypercortisolemic HIV patients, while it is activated in cortisol-resistant HIV patients. This is suggestive of a cytokine system intimately linked with cortisol and its receptors. Highly active antiretroviral therapy is an important advance in the treatment of HIV infection, but the suppression of viral replication is not associated with reconstitution of the immune function. This would account for reduced control of inflammation and the activation of 11ß-hydroxysteroid dehydrogenase type 1(11ß-HSD1) and increases in glucocorticoid and mineralocorticoid production in peripheral tissues. Such hormonal activation may cause insulin resistance and cardiometabolic complications. Therapeutic approaches with 11ß-HSD1 inhibitors, aldosterone antagonists, type 1 angiotensin receptor blockers, or renin inhibitors are suggested.

[Glucocorticoid hormones and the immune response]. / Gliukokortikoidnye gormony i immunnyi otvet.

The level of glyco- and mineralcorticoids in the blood and correlations between functional activity of hypothalamo-hypophyseal--adrenocortical system and antibody production, were investigated. The role of glycocorticoids in the immune system responses to antigen on the cellular and molecular levels including the changes in glycocorticoid binding sites and cyclo-nucleotides level, was shown. The role of glycocorticoids in actualization of the immune responses depending on the intensity and duration of hormonal changes, is considered from the standpoint of different sensitivity of the individual clones of immunocompetent cells to hormones.