PATHOGENETIC ROLE, IN HUMAN AND MURINE TUBERCULOSIS, OF CHANGES IN THE PERIPHERAL METABOLISM OF GLUCOCORTICOIDS AND ANTIGLUCOCORTICOIDS

Citation
Gaw. Rook et R. Hernandezpando, PATHOGENETIC ROLE, IN HUMAN AND MURINE TUBERCULOSIS, OF CHANGES IN THE PERIPHERAL METABOLISM OF GLUCOCORTICOIDS AND ANTIGLUCOCORTICOIDS, Psychoneuroendocrinology, 22, 1997, pp. 109-113
Citations number
30
Categorie Soggetti
Neurosciences,"Endocrynology & Metabolism
Journal title
ISSN journal
03064530
Volume
22
Year of publication
1997
Supplement
1
Pages
109 - 113
Database
ISI
SICI code
0306-4530(1997)22:<109:PRIHAM>2.0.ZU;2-F
Abstract
Immunity to tuberculosis (TB) requires a Th1 pattern of cytokine relea se, dominated by interleukin-2 (IL-2) and interferon gamma (IFN gamma) . In experimental models even a minor Th2 component (characterized by production of IL-4) abrogates immunity, and leads to an immunopatholog y that mimics the human disease. Increased exposure of T cells to gluc ocorticoids drives them towards a Th2 cytokine profile and could there fore help to explain the presence of an inappropriate Th2 component in TB. Analysis of adrenal steroid metabolites in 24-h urine collections revealed a striking increase in metabolites of active cortisol relati ve to metabolites of inactive cortisone. This indicates a change in th e balance of 11 beta-hydroxysteroid dehydrogenase to 11 beta-ketostero id reductase. The site of this disease-associated alteration in reduct ase/dehydrogenase balance may be the lung. The lung contains 11 beta H SD-1, (a reversible oxido-reductase) which in the liver works as a red uctase. In the normal lung it functions paradoxically as a reductase, but it can alter its function in the presence of cytokines. TB patient s (like other ill individuals) also show reduced 24-h urinary secretio n of dehydroepiandrosterone (DHEA) derivatives. Since these have antig lucocorticoid functions in vivo, this fall may exacerbate the effects of the reduced inactivation of cortisol and loss of diurnal rhythm, an d contribute to immunological dysfunction. Recent studies of TB in mic e, and in children during infancy, adrenarche and puberty, suggest tha t the ratio of cortisol to DHEA may be crucial both to susceptibility and to the pathology of the disease that develops. (C) 1997 Elsevier S cience Ltd.