Alteration of the cortisol-cortisone shuttle in leprosy type 1 reactions in leprosy patients in Hyderabad, India.
Regulation of inflammation in leprosy may be influenced by local concentrations of active cortisol and inactive cortisone, whose concentrations are regulated by enzymes in the cortisol-cortisone shuttle. We investigated the cortisol-cortisone shuttle enzymes in the skin of leprosy patients with type 1 reactions (T1R), which are characterised by skin and nerve inflammation. Gene expression of the shuttle enzymes were quantified in skin biopsies from 15 leprosy patients with new T1R before and during prednisolone treatment and compared with levels in skin biopsies from 10 borderline leprosy patients without reactions. Gene expression of 11beta-hydroxysteroid dehydrogenase (11beta-HSD) type 2, which converts cortisol to cortisone, is down-regulated in skin from T1R lesions. However expression levels of 11beta-HSD type 1, which converts cortisone to cortisol, were similar in skin with and without reactions and did not change during anti-leprosy drug treatment. Prednisolone treatment of patients with reactions is associated with an upregulation of 11beta-HSD2 expression in skin. The down regulation of 11beta-HSD2 at the beginning of a reaction may be caused by pro-inflammatory cytokines in the leprosy reactional lesion and may be a local attempt to down-regulate inflammation. However in leprosy reactions this local response is insufficient and exogenous steroids are required to control inflammation.
Andersson
Anna K
AK
Department of Infectious & Tropical Diseases, London School of Hygiene & Tropical Medicine, London WC1E 7HT, UK.
Atkinson
Sara E
SE
Khanolkar-Young
Saroj
S
Chaduvula
Mehervani
M
Jain
Suman
S
Suneetha
Lavanya
L
Suneetha
Sujai
S
Lockwood
Diana N J
DN
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D003348:Cortisone / Q000276:immunology / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D006854:Hydrocortisone / Q000276:immunology / Q000378:metabolism*; D007194:India; D015439:Leprosy, Borderline / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D011239:Prednisolone / Q000276:immunology
D011239:Prednisolone; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; D003348:Cortisone; D006854:Hydrocortisone