LIPOSOMAL DEXAMETHASONE EFFECTIVENESS IN THE TREATMENT OF HYPERSENSITIVITY PNEUMONITIS IN MICE

The effects of daily intranasal instillation of liposomal dexamethason e and free dexamethasone phosphate were compared in a murine model of hypersensitivity pneumonitis induced by Saccharopolyspora rectivirgula (formally known as Micropolyspora faeni). After 3 weeks of antigen an d liposome instillations, lung response was evaluated by bronchoalveol ar lavage cell counts, lung index and histopathology. Systemic absorpt ion was evaluated by measuring plasma adrenocorticotropic hormone (ACT H) level. Free dexamethasone phosphate induced a dose-dependent respon se with the maximal effect reached at 1 mg kg-1. At 0.1 mg kg-1, lipos omal dexamethasone had a greater effect than free dexamethasone phosph ate on bronchoalveolar cells ml-1: 3.01 x 10(5) +/- 0.35 x 10(5) compa red to 4.70 x 10(5) +/- 0.34 x 10(5), and lung index: 1.22 +/- 0-10 co mpared to 1.86 +/- 0.07. Effect on histopathology was similar. Plasma ACTH levels (pg ml-1) were: 75.1 +/- 14.0 for animals receiving antige n and free dexamethasone phosphate (0.2 mg kg-1), and 149.7 +/- 12.0 f or animals receiving antigen and liposomal dexamethasone (0.2 mg kg-1) . In conclusion, liposome-incorporated dexamethasone is efficient in t he treatment of experimental hypersensitivity pneumonitis and, contrar ily to free dexamethasone phosphate, does not inhibit ACTH secretion.