Leffler J, Abad A, Short B, Lauzon-Joset J, Holt PG, Strickland DH
The Kids Research Institute Australia, The University of Western Australia, Perth Australia
After puberty allergic asthma converts from a disease that mainly affects boys to a disease with a higher prevalence in females who also suffer from more severe symptoms. This transition suggests a crucial role for the female sex hormones in disease pathology. Interestingly, we have previously observed a similar relation in our experimental asthma rat model consisting of two-rat strains with different susceptibility to chronic respiratory disease. To identify if estrogen is the causative agent for the high-susceptibility phenotype, we used slow releasing estrogen pellets inserted into male rats and managed to induce a disease phenotype analogous to the females with more severe asthma exacerbations. Interestingly this was only observed in one of the two rat strains, used in the model, that is characterized by chronic respiratory disease compared to the other strain characterized by resistance to chronic disease. In 2016 we will investigate the immunological mechanisms relating to the observations. We will also map the immunological differences in between male and females in our model and how estrogen exposure alters the immunological balance. The model is clinically relevant given that the same phenotype is observed in humans. In addition, the effect of estrogen appears dependent on genetic background since the influence is only evident in the strain that is also susceptible to chronic disease.
Plain language summary: Based on human population studies on allergies and asthma, it is apparent that after puberty females suffer more often and more severely from these diseases compared to males. To identify the immunological reason for this we have designed a study to investigate how the female sex hormone, estrogen, affects asthma exacerbations. The study aims to identify the mechanism for this so that this knowledge can be used to better treat asthma and allergies in both males and females.
Funder: Asthma Foundation of Western Australia