acth-(7-38) and Mycoses

Three aspects of the possible relationships between adrenocortical function and mycoses are considered: a) abnormal steroid hormone concentrations that may favour onset and/or clinical course of mycotic diseases; b) presence of granulomas in the adrenal glands during systemic mycoses; c) effects of antifungal drugs on steroidogenesis. Glucocorticoids are potent inhibitors of T-lymphocyte proliferation, in that they affect both the production of IL-1 from monocytes/macrophages and IL-2 from activated T-lymphocytes. Consequently opportunistic fungal infections are frequently observed in patients with chronic hypercortisolism (Cushing's syndrome) and in particular in those under chronic treatment with corticoids. On the other hand, mucocutaneous candidiasis is a prominent feature of the autoimmune polyglandular syndrome type I, characterized by adrenal insufficiency, hypoparathyroidism and mucocutaneous candidiasis. Its onset is usually at childhood, first with symptoms and signs of the fungal infection and then with those of endocrine failure. It is a complex disorder, familiar or sporadic, not linked to particular HLA haplotype, potentially associated with other autoimmune diseases (endocrine and not), thus forming the so called candidiasis endocrinopathy syndrome (CES). Adrenal involvement is very frequent in systemic mycoses, such as histoplasmosis (Histoplasma capsulatum), cryptococcosis (Cryptococcus neoformans), and paracoccidioidomycosis. From the pathogenetic view point, corticostatins-defensins may play a role. They are a family of recently discovered cationic peptides, that are able to inhibit adrenal steroidogenesis by interfering with ACTH at the specific receptor level. The pharmacological effects of ketoconazole on adrenal (and gonadal) steroidogenesis are a focus of great interest. This compound has been demonstrated to be a potent inhibitor of cytochrome P450-dependent enzymes.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Acquired Immunodeficiency Syndrome; Adrenal Cortex Hormones; Adrenal Glands; Adrenal Insufficiency; Amino Acid Sequence; Antifungal Agents; Candidiasis; Cushing Syndrome; Disease Susceptibility; Female; Humans; Incidence; Intercellular Signaling Peptides and Proteins; Ketoconazole; Male; Molecular Sequence Data; Mycoses; Opportunistic Infections; Peptides; Structure-Activity Relationship