Ruolo dell'immunità e degli ormoni sessuali in un modello di anno epatico acuto

Direct and indirect effect of sex hormones have been demonstrated to control the inflammation process. Using animal models of tissue damage, androgens demonstrated to be immunosuppressive while estrogens contributed to exert immunoprotective activity and wound repair. As liver regeneration showed to be slower and more difficult in males than in females, in this thesis a liver acute damage model was obtained by injection of CCl4 in Balb/c mice (males and females). By cytometrical multiparametric method, the endogenous and exogenous populations of monocyte and lymphocyte lineages were explored. The expression level of target markers, relative to cells of healthy animals, was assumed as reference to discriminate the immunoreactivity of test groups of liver damage. In order to define the regulatory role of androgens on the liver acute damage response, some animals were also treated with an antagonist of androgen receptor (AR), flutamide. The flutamide effect on liver endogenous and exogenous cells was defined as specific when compared to that of oil vehicle. The cytometrical study showed important differences among males and females. In particular, the homing time of immunosuppressive myeloid cells was delayed in males in respect to females. Moreover, the homing resulted to be dependent on androgens as the inhibition of AR through flutamide tackled migrating Gr-1high cells to liver. While flutamide showed to contribute to inflammation in males, in contrast it guaranteed its negative regulation in females.