Immunoendocrine interactions during chronic cysticercosis determine male mouse feminization: Role of IL-6

Taenia crassiceps cysticercosis results in an Impressive feminization in ma le mice during chronic infection, characterized by increased serum estradio l levels 100 times their normal values, while those of testosterone and dih ydrotestosterone are decreased by 85 and 95 % respectively. Concomitantly, the levels of follicle-stimulating hormone and IL-6 are increased 70 and 90 times their normal values in the infected male mice. Since a specific Th1/ Th2 shift of the immune response has been previously reported during the ch ronic infection, and this shift may be associated with the feminization pro cess, we proposed that this shift is induced by immunoendocrine interaction s during the disease, and this gives way to a change in the initial resista nce to the infection in the male mice, which become as susceptible as femal e mice. To confirm this hypothesis, we depleted immune system activity in t wo different ways: total body irradiation and neonatal thymectomy. Our resu lts show that when immune system activity is depleted using either strategy , the male mice do not feminize, and the levels of follicle-stimulating hor mone and IL-6 are inhibited. Depletion of IL-6 using IL-6(-/-) knockout mic e does not produce the feminization process stated above, while restitution of the IL-6(-/-) knockout, irradiated, and thymectomized mice with murine recombinant IL-6 restores the feminization process. Expression of the IL-6 gene was found only in the testes and spleen of infected animals. Our resul ts illustrate the importance of immunoendocrine interactions during a paras itic disease and show a possible new mechanism of parasite establishment in an initially resistant host.