Journal of AIDS & Clinical Research

Cross-Talk among Glucocorticoids, Glucocorticoid Receptors and Cytokines Pilots Inflammatory, Endocrine, Immune and Metabolic Responses in HIV Infection

Abstract

Guido Norbiato

A number of diseases including viral and bacterial infections, inflammatory and auto-immune disorders is associated with glucocorticoids resistance. Tissue resistance to glucocorticoids is observed in untreated HIV infected patients with hypercortisolism. These patients show a complete inability of glucocorticoids to exert their effect, full Addisonian symptoms and an impressive increase in type-1 Th-directed cellular immunity. This clearly suggests a severe receptor resistance to glucocorticoids. Removal of glucocorticoids by adrenal insufficiency or decreased glucocorticoid receptors sensitivity, likely induced by HIV RNA, endotoxin and lipopolysaccarides, significantly enhances morbidity and mortality in such patients. Highly active antiretroviral therapy is an important advance in the treatment of HIV infection since confers survival and acceptable conditions of life, but the suppression of viral replication is not associated with reconstitution of the immune function. This allows persistence of chronic inflammatory disease and activation of local 11β hydroxy steroid dehydrogenase type-1 and type-2 with associated increases in glucocorticoids and mineralcorticoids production. Glucocorticoids and their receptors have a central role in the control of innate and adaptive immune responses. In turn, cytokines signaling pathway may influence neuroendocrine function through changes in the receptors sensitivity and function. Evidence shows that glucocorticoids system works in concert with other systems, including the immune, metabolic and renin-angiotensin aldosterone systems. Imbalance of this network mainly drives to chronic inflammation and the metabolic syndrome with its component of insulin resistance, dyslipidemia and cardiovascular complications. Therapeutic strategies to restore the integrity of glucocorticoid receptor function and reconstitute the immune function are needed to keep HIV infected patients away from complications. Current therapeutic approaches tend to inhibit the 11β hydroxy steroid dehydrogenase type-1 activity and the renin-angiotensin-aldosterone system function. Both these treatments may reduce inflammation