Effect of oestrogen on Mycobacterium avium complex pulmonary infection in mice

The purpose of the present study was to elucidate the role of oestrogen in the pathogenesis of Mycobacterium avium complex (MAC) pulmonary disease, wh ich occurs most frequently in postmenopausal women. The study was carried o ut in a murine infectious model using ovariectomized DBA/2 female mice. Inf ection with MAC was established by intratracheal administration of bacilli. In some experiments, ovariectomized mice were treated with exogenous 17 be ta -estradiol (E2). The number of bacilli in the lungs of infected mice whi ch received ovariectomy was significantly larger than that in the lungs of sham-operated control mice, and treatment of ovariectomized mice with exoge nous E2 restored the burden of bacilli to the same level as that in the sha m-operated control mice. We next examined the effect of E2 in vitro using b one marrow-derived macrophages obtained from DBA/2 female mice. The macroph ages showed bacteriostatic activity against MAC after treatment with interf eron-gamma (IFN-gamma) and this activity was further enhanced by the exogen ous addition of E2 to the culture medium. In parallel with these findings, E2 augmented the production of reactive nitrogen intermediates (RNI) by mac rophages pretreated with IFN-gamma and stimulated with MAC, as shown by eva luating nitrite production and inducible nitric oxide synthase mRNA express ion. These findings taken together suggest that absence of endogenous oestr ogen appears to be responsible for the development of MAC pulmonary disease in this mouse model and that the enhancement by E2 of anti-MAC activity of murine macrophages induced through increased RNI production may play some role in resistance to MAC infection.