The attenuated androgen Danazol can partially reverse the biochemical defect and prevent angioedema in patients with inherited C1-inhibitor (C1-INH) deficiency (hereditary angioedema, HAE). Though its clinical effectiveness is independent from significant increase of C1-INH plasma levels, its mechanism of action remains unknown. Since angioedema is a local phenomenon, it could be controlled by restoring tissue levels of C1-INH. We measured the expression of C1-INH mRNA in peripheral blood mononuclear cells (PBMCs) of 13 patients with HAE type 1 (seven untreated and asymptomatic, and six on Danazol at the minimal effective dose) and of eight normal controls. mRNA levels were quantitated by computerized optical densitometry of reverse transcriptase-PCR products, normalized for the amount of glyceraldehyde-3-phosphate-dehydrogenase and expressed as percent of normal pooled RNAs. Each determination represented the mean of three separate experiments. Measurement of C1-INH mRNA in two patients before and after 1 month of Danazol 400 mg per day demonstrated a post-treatment increase of 15 and 21%, respectively. When HAE patients and controls were analyzed as groups, C1-INH mRNA levels of patients untreated and asymptomatic (median 73%, range 65-78) were significantly lower (P=0.001) compared to controls (median 101%, range 87-121) and to patients on Danazol (median 91%, range 82-96); the difference among the last two groups was not statistically significant. Our data demonstrate that minimal effective doses of Danazol increase the expression of C1-INH mRNA in PBMC of HAE patients even in the absence of a significant increase of C1-INH plasma levels.
Increased expression of C1-inhibitor mRNA in patients with hereditary angioedema treated with Danazol / E. Pappalardo, L.C. Zingale, M. Cicardi. - In: IMMUNOLOGY LETTERS. - ISSN 0165-2478. - 86:3(2003 May 01), pp. 271-276.
|Titolo:||Increased expression of C1-inhibitor mRNA in patients with hereditary angioedema treated with Danazol|
|Parole Chiave:||Androgens; Danazol; Hereditary angioedema; Monocytes/macrophages; mRNA|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||1-mag-2003|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/S0165-2478(03)00029-4|
|Appare nelle tipologie:||01 - Articolo su periodico|