Thalidomide attenuates airway hyperresponsiveness and eosinophilic inflammation in a murine model of allergic asthma.
Asthma is characterized by chronic eosinophilic inflammation and hyperresponsiveness of the airways. We hypothesized that thalidomide, which has numerous immunomodulatory properties, may have anti-inflammatory effects in allergic asthma. BALB/c mice sensitized and challenged with ovalbumin (OVA) were treated orally with thalidomide (30, 100, or 300 mg/kg) or a vehicle. When thalidomide was administered to OVA-challenged mice, the number of eosinophils in bronchoalveolar lavage fluid (BALF) was significantly decreased. The numbers of inflammatory cells other than eosinophils were not reduced by thalidomide. Thalidomide inhibited the elevated levels of interleukin-5 (IL-5) and tumor necrosis factor-alpha (TNF-alpha) in BALF by OVA challenges. Histological analysis of the lung revealed that both the infiltration of inflammatory cells and the hyperplasia of goblet cells were significantly suppressed by thalidomide treatment. Furthermore, thalidomide significantly inhibited the response to methacholine induced by OVA challenges. Taken together, thalidomide treatment decreased airway inflammation and hyperresponsiveness in a murine model of allergic asthma. These results might provide an opportunity for the development of novel therapeutics to treat severe asthma.
Asano
Toshiaki
T
Department of Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya, Japan. toshiasa@med.nagoya-u.ac.jp
Kume
Hiroaki
H
Taki
Fumitaka
F
Ito
Satoru
S
Hasegawa
Yoshinori
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D016535:Bronchial Hyperreactivity / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001992:Bronchoalveolar Lavage Fluid; D004195:Disease Models, Animal; D004804:Eosinophils / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D020397:Goblet Cells / Q000473:pathology; D006965:Hyperplasia; D007249:Inflammation / Q000188:drug therapy; D015848:Interleukin-5 / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016210:Methacholine Chloride / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D013792:Thalidomide / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D015848:Interleukin-5; D014409:Tumor Necrosis Factor-alpha; D016210:Methacholine Chloride; D013792:Thalidomide; D010047:Ovalbumin