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, which occurs most frequently in postmenopausal women. The study was carried out in a murine infectious model using ovariectomized DBA/2 female mice. Infection with MAC was established by intratracheal administration of bacilli. In some experiments, ovariectomized mice were treated with exogenous 17 beta-estradiol (E2). The number of bacilli in the lungs of infected mice which received ovariectomy was significantly larger than that in the lungs of sham-operated control mice, and treatment of ovariectomized mice with exogenous E2 restored the burden of bacilli to the same level as that in the sham-operated control mice. We next examined the effect of E2 in vitro using bone marrow-derived macrophages obtained from DBA/2 female mice. The macrophages showed bacteriostatic activity against MAC after treatment with interferon-gamma (IFN-gamma) and this activity was further enhanced by the exogenous addition of E2 to the culture medium. In parallel with these findings, E2 augmented the production of reactive nitrogen intermediates (RNI) by macrophages pretreated with IFN-gamma and stimulated with MAC, as shown by evaluating nitrite production and inducible nitric oxide synthase mRNA expression. These findings taken together suggest that absence of endogenous oestrogen 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.