This study evaluated the effect of cyclosporin-A (CyA), a potent immunosuppressive drug, on Bleomycin (Bleo)-induced pulmonary inflammation in hamster. Pulmonary injury was induced by a single intratracheal (IT) instillation of Bleo. Four groups of 10 male Syrian hamsters each received one of four treatments: (1) IT Bleo and daily intraperitoneal (IP) injections of CyA starting 1 day before IT instillation of Bleo (Bleo-CyA); (2) IT Bleo and IP injections of saline (Bleo-Sal); (3) IT saline and IP CyA (Sal- CyA); (4) IT saline and IP saline (Sal-Sal). Animals were sacrificed 14 days after IT treatment. Lung injury was evaluated histologically, biochemically, and by analysis of bronchoalveolar lavage (BAL) fluid. Treatment of hamsters with CyA significantly ameliorated the severity and extent of the injury on a scale of 0- 3. Lung hydroxyproline measurements were lower in Bleo-CyA compared to Bleo-Sal, comparable to Sal-Sal and Sal-CyA controls. The percentage of neutrophils, eosinophils, and lymphocytes in BAL fluid was higher in Bleo-Sal and Bleo-CyA animals when compared with control Sal-CyA or Sal-Sal animals. A further increased in percentage of eosinophils was observed in Bleo-CyA compared with Bleo-Sal animals (13.3 ±6.6% [mean ± SE] and 3.7 ± 2.1%, respectively, p = .0007). BAL fluid protein content was higher in Bleo-Sal compared to Sal-Sal animals, but BAL fluid protein content was higher in Bleo-CyA was not significantly different from that of Bleo-Sal animals. These results indicate that CyA ameliorates the Bleo-induced inflammation but does not prevent leakage of plasma protein or cells into the airspaces. The increased eosinophil numbers in Bleo-CyA-treated hamsters suggests enhanced production of interleukin-4 and -5.
- cyclosporin A
- interstitial lung disease
ASJC Scopus subject areas
- Pulmonary and Respiratory Medicine