Effects of cyclosporin A by aerosol on airway hyperresponsiveness and inflammation in guinea pigs.
OBJECTIVE
To study cyclosporin A (CsA) by aerosol for anti-asthmatic effects in guinea pigs.


METHODS
PC200 changes of lung resistance (RL) in the antigen-challenged sensitized guinea pig induced by acetylcholine (ACh) or histamine, and eosinophils changes in bronchoalveolar lavage fluid (BALF) and pulmonary histologic section induced by antigen in vivo in sensitized guinea pigs were investigated.


RESULTS
Pretreatment with CsA 10 g/L and 20 g/L by aerosol but not with CsA 5 g/L, dexamethasone (DXM) 0.5 mg/kg by ip increased PC200 value and prevented ACh or histamine-induced airway hyperresponsiveness. However, CsA 5 g/L also prevented histamine-induced airway hyperresponsiveness. CsA 10 g/L, 20 g/L and DXM 0.5 mg/kg reduced markedly eosinophil accumulation in BALF. The lymphocyte accumulation induced by antigen was not changed significantly by CsA and DXM tested. DXM 0.5 mg/kg increased number of neutrophil in the BALF. There was a statistical significance comparison with CsA groups. In the pulmonary histological studies, CsA 20 g/L and DXM 0.5 mg/kg also inhibited eosinophil infiltration in the epithelium and subepithelial connective tissue of bronchi and bronchioles.


CONCLUSIONS
Anti-inflammation and anti-hyperresponsiveness of CsA by aerosol in animal model offered an experimental evidence for airway inhalation of CsA in the treatment of asthma.
Xie
Qing-Min
QM
Zhejiang Respiratory Drugs Research Laboratory of State Drugs Administration of China, Medical School of Zhejiang University, Hangzhou 310031, China. Xieqm@zju.edu.cn
Chen
Ji-Qiang
JQ
Shen
Wen-Hui
WH
Yang
Qiu-Huo
QH
Bian
Ru-Lian
RL
D000109:Acetylcholine; D000336:Aerosols; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000627:therapeutic use*; D001249:Asthma / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D018893:Bronchoalveolar Lavage; D016572:Cyclosporine / Q000494:pharmacology*; D003907:Dexamethasone / Q000627:therapeutic use*; D004357:Drug Synergism; D004804:Eosinophils / Q000187:drug effects* / Q000473:pathology; D005260:Female; D006168:Guinea Pigs; D006632:Histamine; D007166:Immunosuppressive Agents; D008297:Male; D010047:Ovalbumin
D000336:Aerosols; D018927:Anti-Asthmatic Agents; D007166:Immunosuppressive Agents; D003907:Dexamethasone; D006632:Histamine; D016572:Cyclosporine; D010047:Ovalbumin; D000109:Acetylcholine