Inhalation of N-Chlorotaurine Is an Effective Treatment of Aspergillus fumigatus Pneumonia in Mice
Abstract
Abstract Introduction N-chlorotaurine (NCT), a long-lived oxidant of human granulocytes, can be used topically as anti-infective in different body regions. The aim of the present study was to demonstrate the efficacy and tolerability of inhaled NCT in a mouse model of Aspergillus fumigatus pneumonia. Methods Specific pathogen-free female C57BL/6JRj mice were immune-suppressed with cyclophosphamide or cortisone acetate. After 7 days, they were inoculated intranasally with 6.5 × 106 spores of A. fumigatus. Treatment with aerosolized (<5 µm) aqueous 0.1%, 0.5%, 1.0%, or 2.0% NCT solution or 0.9% sodium chloride as placebo three times daily for 10 min was started 1 h after inoculation and ended after 14–16 days. Prophylactic treatment exclusively for 2 days before infection was investigated additionally. Main parameters of evaluation were survival and fungal load in the lung homogenate, secondary ones clinical (body weight, organ weights, body temperature) and blood inflammation parameters, bronchoalveolar lavage fluid analysis, and histology of organs. Results Pneumonia occurred in all mice, but the survival was much higher in animals treated with NCT compared to placebo. In placebo groups, 8/9 mice observed for 15 days died from the infection during this time, while 0/9 to 1/9 died in groups treated with 0.5%, 1.0%, and 2.0% NCT (p < 0.01 for each concentration versus saline). There was no difference between the two ways of immune-suppression. With 0.1% NCT, 4/9 mice died (p =…
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