Cyclosporin A protects lung function from hyperoxic damage

Cyclosporin A (CsA), an inhibitor of protein phosphatase 2B (calcineurin), has been shown to play a role in exocytosis and neutrophil mobility. Hypero xia (>95% oxygen for 72 h) causes lung injury and reduces lung compliance. This model is indicative of deficiencies in surfactant and elicits a vigoro us immune response leading to further damage. We examined the effects of Cs A on surfactant-secreting lung alveolar type II cells. CsA enhances ATP-sti mulated increases in whole cell capacitance in the presence of 2 mM extrace llular Ca2+. This measurement corresponds with increases in exocytosis. Bec ause of its effect on the immune system and exocytosis from type II cells, CsA was examined for its protective effects against hyperoxia-induced lung damage in mice. We found that CsA (50 mg.kg(-1).day(-1)) attenuated hyperox ia-induced reductions in lung compliance when administered before or during 72 h of >95% oxygen (P < 0.05). CsA (10 mg.kg(-1).day(-1)) also had a prot ective effect against hyperoxia-induced changes in neutrophil infiltration, capillary congestion, edema, and hyaline membrane formation. Wet lung weig ht-to-dry lung weight ratios did not show any significant changes after hyp eroxia or hyperoxia plus CsA (P < 0.05). CsA may be useful to treat patient s undergoing prolonged high-oxygen therapy and possibly other lung injuries .