Progesterone and environmental tobacco smoke act synergistically to exacerbate the development of allergic asthma in a mouse model.

摘要

BACKGROUND: Asthma affects males and females differently. Females have a higher incidence than males after the onset of puberty. This suggests a hormonal component to the development of the disease. Progesterone, a female hormone, has previously been shown to illicit a T-helper type 2 (TH2) immune response similar to that seen in allergic asthma. Previous studies performed by our laboratory have shown that exposure to environmental tobacco smoke (ETS) enhances the immune response to allergens. OBJECTIVE: To determine if the combination of exposure to ETS and progesterone would further exacerbate the immune response in a mouse model of allergic asthma. METHODS: Female mice were ovariectomized and then implanted with time-release progesterone pellets. Mice were housed in either filtered air (FA) or ETS chambers and half were exposed to aerosolized house dust mite allergen (HDMA). Bronchoalveolar lavage was performed for cell differentials; lung and spleen cells were harvested to compare IL-4 and IFN-gamma production by ELISPOT. RESULTS: Progesterone pellet implantation resulted in increased serum progesterone levels (28.3+/-8.43 vs. 13.5+/-7.22 ng/mL in placebo-treated mice, P<0.0001). Serum total IgE levels were significantly greater in progesterone vs. non-progesterone treated animals that were also exposed to HDMA. ETS exposure enhanced total IgE levels as well. Lung homogenate cells from HDMA/progesterone-treated animals stimulated with Concavalin A produced significantly more IL-4 compared with HDMA/placebo-treated animals (200+/-17.6 vs. 146+/-17.5 spots/well, P<0.01 in ETS exposed animals and 221+/-28.9 vs. 167+/-23.4 spots/well, P<0.01 in animals housed in FA). HDMA/ETS-treated animals had higher eosinophilia in lavage than all other groups. CONCLUSION: Increased serum progesterone levels exacerbate the allergic asthmatic phenotype in a mouse model. These effects are further exacerbated by the addition of environmental tobacco smoke. Progesterone provides a major contribution to the gender differences seen in the development and elicitation of the asthmatic response.