Clin Exp Otorhinolaryngol.  2016 Dec;9(4):332-338. 10.21053/ceo.2015.01599.

Effect of Long-Term Antiorthostatic Suspension in a Murine Model of Acute Lung Injury

Affiliations
  • 1Department of Otorhinolaryngology-Head and Neck Surgery, Inha University School of Medicine, Incheon, Korea. inhaorl@inha.ac.kr

Abstract


OBJECTIVES
Antiorthostatic suspension (AOS) is ground-based model of simulated microgravity. There is still no study about the effect of long-term microgravity on the clinical course of acute lung injury. We evaluated the effect of simulated microgravity using AOS in a murine model of acute lung injury by lipopolysaccharide (LPS).
METHODS
Thirty BALB/c mice were used. During 4 weeks, mice were equally allocated to control (free movement), restraint (tail suspended, but hindlimbs not unloaded), and AOS group (hindlimb unloaded). After then, mice got intranasal challenge with LPS (20 mg/kg, 50 μL). We measured: weight gain before and after AOS, the number of inflammatory cells and titers of cytokines (interleukin [IL]-1β, IL-6, IL-10, tumor necrosis factor-α, and interferon-γ) in bronchoalveolar lavage (BAL) fluid, titer of myeloperoxidase (MPO) in serum and lung homogenate, and histopathologic examination of lung tissue.
RESULTS
AOS group had significant weight loss compared to control and restraint group (P<0.001). AOS group also showed significantly decreased lymphocytes (P=0.023) compared to control group. In AOS group, titer for IL-1β in BAL fluid was significantly lower than restraint group (P=0.049). Titer for serum MPO was significantly decreased in AOS group compared to restraint group (P=0.004). However, there was no significant difference of MPO titers in lung tissue between groups. Histopathologic examination of lung tissue revealed no significant difference in the degree of pulmonary infiltration between restraint and AOS group.
CONCLUSION
In spite of modest anti-inflammatory effect, prolonged AOS caused no significant change in LPS-induced pulmonary inflammation.

Keyword

Hindlimb Suspension; Lipopolysaccharides; Acute Lung Injury

MeSH Terms

Acute Lung Injury*
Animals
Bronchoalveolar Lavage
Cytokines
Hindlimb
Hindlimb Suspension
Interleukin-10
Interleukin-6
Lipopolysaccharides
Lung
Lymphocytes
Mice
Necrosis
Peroxidase
Pneumonia
Weight Gain
Weight Loss
Weightlessness
Cytokines
Interleukin-10
Interleukin-6
Lipopolysaccharides
Peroxidase

Figure

  • Fig. 1. Weight gain after 4 weeks. Control group: free movement without tail suspension. Restraint group: tail suspended, but hindlimb not unloaded. Antiorthostatic suspension (AOS) group: hindlimb unloaded by tail suspension. Error bar: standard deviation. KruskalWallis and Mann-Whitney U-tests. ***P<0.001.

  • Fig. 2. Number of neutrophils (A), lymphocytes (B), and macrophages (C) in bronchoalveolar lavage (BAL) fluid after intranasal challenge with lipopolysaccharide. Control group: free movement without tail suspension. Restraint group: tail suspended, but hindlimb not unloaded. Antiorthostatic suspension (AOS) group: hindlimb unloaded by tail suspension. Error bar: standard deviation. KruskalWallis and Mann-Whitney U-tests. ***P<0.001.

  • Fig. 3. Titers for interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, and interleukin (IFN)-γ in bronchoalveolar lavage (BAL) fluid after intranasal challenge with lipopolysaccharide. Control group: free movement without tail suspension. Restraint group: tail suspended, but hindlimb not unloaded. Antiorthostatic suspension (AOS) group: hindlimb unloaded by tail suspension. Error bar: standard deviation. ***P<0.001.

  • Fig. 4. Titer for serum myeloperoxidase (MPO; A) and MPO titer in lung homogenate (B). Control group: free movement without tail suspension. Restraint group: tail suspended, but hindlimb not unloaded. Antiorthostatic suspension (AOS) group: hindlimb unloaded by tail suspension. Error bar: standard deviation. Kruskal-Wallis and Mann-Whitney U-tests. ***P<0.001.

  • Fig. 5. (A) Histopathologic examination of lung tissue (H&E, ×200; 50 μm). (B) Number of infiltrated neutrophils in 1 mm2 of lung parenchyme. Control group: free movement without tail suspension. Restraint group: tail suspended, but hindlimb not unloaded. Antiorthostatic suspension (AOS) group: hindlimb unloaded by tail suspension. Error bar: standard deviation. ***P<0.001.


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