BACKGROUND: Hind limb unloading (HU) is one of the ground-based models of simulated microgravity. As bacterial and viral infections could affect the immune system, the immunologic effect of HU should be studied in a specific-pathogen-free (SPF) laboratory. However, a review of the literature did not reveal any studies on the immunologic effects of prolonged HU in a murine model of allergic disease. Accordingly, the present study was undertaken to evaluate the effect of HU in a murine model of allergic asthma in a SPF laboratory.METHODS: Twenty BALB/c mice were allocated equally to Group A (control group), Group B (HU group), Group C (allergic group), or Group D (allergic + HU group). Weight gains, serum total and ovalbumin (OVA)-specific IgE, titers of IL-1, IL-5, IL-10, and IFN-γ in bronchoalveolar lavage (BAL) fluid, and histopathologic findings of the lungs were compared.RESULTS: After 2 wk of HU, Group D showed significantly more weight loss (−2.0 ± 0.2 g) than Group C (−1.1 ± 0.4 g). Groups B and D showed significant increases in serum OVA-specific IgE as compared with Groups A and C. Group D had significantly lower titers of IL-5 (Group C: 53.0 ± 15.2 pg · ml⁻¹, Group D: 21.9 ± 13.9 pg · ml⁻¹), IL-10 (Group C: 430.8 ± 138.3 pg · ml⁻¹, Group D: 217.6 ± 51.2 pg · ml⁻¹), and IFN-γ (Group C: 104.3 ± 37.5 pg · ml⁻¹, Group D: 36.7 ± 12.8 pg · ml⁻¹) in BAL fluid than Group C. Peri-bronchiolar and pulmonary infiltrations of inflammatory cells were significantly greater in Group D than in Group C.CONCLUSIONS: Prolonged HU may cause significant weight loss and aggravate disease courses.Jang TY, Heo M-J, Jung A-Y, Kim YH. Prolonged anti-orthostatic hind limb unloading and murine allergic asthma. Aerosp Med Hum Perform. 2015; 86(9):803–807.