Objective: To determine whether allergic pulmonary inflammation is causatively linked to an increase in the rate of metastasis to the lung and if administration of a commonly prescribed therapy to control the inflammation associated with allergic asthma (i.e., inhaled corticosteroids) attenuates the increase in lung metastasis.

Methods: A B16F10 melanoma model was used to assess lung metastasis to the lungs as a function of allergic pulmonary inflammation. Specifically, C57BL/6 mice were subjected to a chronic allergen (chicken ovalbumin (OVA)) exposure protocol: intraperitoneal (i.p) sensitization with OVA followed by OVA aerosol exposures to induce localized TH2 immune responses in the lung. Control animals were administered saline. During the provocation phase of this protocol the mice received a tail vein injection of B16F10 melanoma cells (2 x 105 per animal). The presence and number of developed lung metastases were assessed by gross morphological determinations using a low power 4x stereo-dissecting microscope 12 days later. In addition, two other cohorts of animals were studied. One group of mice was treated with CD4+ T cell-depleting antibody (GK1.5, 0.5mg/injection (i.p.)) and another received the corticosteroid Budesonide intranasally to reduce allergen induced pulmonary inflammation. Control mice received IgG and PBS vehicle alone respectively.

Results: Allergen-induced pulmonary inflammation was associated with a nearly 4-fold increase in lung metastasis. Significantly, the ablation of CD4+ T cells through the concomitant administration of the T cell-depleting antibody GK1.5 abolished allergen-induced pulmonary inflammation and, more importantly, returned the rate of metastasis to allergen naive levels. Likewise, administration of Budesonide resulted in a significant decrease in allergic pulmonary inflammation and lung metastasis, consistent with our hypothesis linking allergen-induced pulmonary inflammation and metastasis.

Conclusions: Our studies demonstrate a link between allergic pulmonary inflammation and an increase in the rates of metastasis to the lung. These data show that a commonly used treatment for the inflammation associated with asthma (i.e., inhaled corticosteroids) effectively reverses the observed increase in lung metastasis. These results suggest that breast cancer patients with a prior diagnosis of asthma may have a greater probability of pulmonary metastasis compared to patients with no history of this chronic lung disease. If translatable to cancer patients with asthma as a preexisting condition, this observation would suggest additional avenues of therapy targeted to the lung.

98th AACR Annual Meeting-- Apr 14-18, 2007; Los Angeles, CA