Chlorine is a highly toxic respiratory
irritant that when inhaled causes epithelial cell injury, alveolar-capillary barrier disruption, airway hyperreactivity,
inflammation, and
pulmonary edema.
Chlorine is considered a chemical threat agent, and its release through accidental or intentional means has the potential to result in mass casualties from
acute lung injury. The type 4
phosphodiesterase inhibitor rolipram was investigated as a rescue treatment for
chlorine-induced
lung injury.
Rolipram inhibits degradation of the intracellular signaling molecule
cyclic AMP. Potential beneficial effects of increased
cyclic AMP levels include inhibition of
pulmonary edema,
inflammation, and airway hyperreactivity. Mice were exposed to
chlorine (whole body exposure, 228-270 ppm for 1 h) and were treated with
rolipram by intraperitoneal, intranasal, or intramuscular (either aqueous or nanoemulsion formulation) delivery starting 1h after exposure.
Rolipram administered intraperitoneally or intranasally inhibited
chlorine-induced
pulmonary edema. Minor or no effects were observed on lavage fluid
IgM (indicative of
plasma protein leakage), KC (Cxcl1, neutrophil
chemoattractant), and neutrophils. All routes of administration inhibited
chlorine-induced airway hyperreactivity assessed 1 day after exposure. The results of the study suggest that
rolipram may be an effective rescue treatment for
chlorine-induced
lung injury and that both systemic and targeted administration to the respiratory tract were effective routes of delivery.