Inhibition of p-450 aromatase prevents feminisation and induces protection during cysticercosis.
Cysticercotic male mice undergo an impressive feminisation process, characterised by 200 times increased serum 17beta-estradiol levels while testosterone and dihydrotestosterone are 90% reduced, which results in elevated parasite burden. Administration of Fadrozole (an aromatase inhibitor) in male and female mice suppressed the production of 17beta-estradiol, accompanied with a 70% reduction in parasite burden. This protective effect was associated in male mice with a recovery of the specific cellular immune response. Interleukin-6 (IL-6) serum levels, and its production by splenocytes, was augmented by 80%, together with a 10-fold increase in its expression in testes of infected male mice. Fadrozole treatment returned these levels to baseline values. Aromatase expression in the testes of infected male mice was not affected by Fadrozole. These results suggest that aromatase and IL-6 are key molecules in the production of the feminisation undergone by infected male mice and to Fadrozole treatment as a possible new therapeutic approach to cysticercosis.
D000818:Animals; D000909:Antibodies, Helminth / Q000276:immunology / Q000302:isolation & purification; D001141:Aromatase / Q000235:genetics; D047072:Aromatase Inhibitors; D003551:Cysticercosis / Q000188:drug therapy* / Q000201:enzymology* / Q000276:immunology / Q000469:parasitology; D004791:Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use*; D004958:Estradiol / Q000096:biosynthesis; D017316:Fadrozole / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005262:Feminization / Q000150:complications / Q000188:drug therapy*; D005786:Gene Expression Regulation / Q000187:drug effects; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013621:Taenia / Q000302:isolation & purification / Q000502:physiology; D013737:Testis / Q000201:enzymology / Q000276:immunology
D000909:Antibodies, Helminth; D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D015850:Interleukin-6; D012333:RNA, Messenger; D004958:Estradiol; D001141:Aromatase; D017316:Fadrozole