Ricin, a highly toxic plant-derived toxin, is considered a potential weapon in biological warfare due to its high availability and ease of preparation. Pulmonary exposure to
ricin results in the generation of an acute edematous
inflammation followed by
respiratory insufficiency and death. Passive immunization with polyclonal anti-
ricin antibodies conferred protection against pulmonary ricinosis, however, at clinically-relevant time points for treatment, survival rates were limited. In this study, intranasal instillation of a lethal dose of
ricin to mice, served as a lung challenge model for the evaluation and comparison of different therapeutic modalities against pulmonary ricinosis. We show that treatment with
doxycycline resulted in a significant reduction of pro-inflammatory
cytokines, markers of oxidative stress and capillary permeability in the lungs of the mice. Moreover, survival rates of mice intoxicated with
ricin and treated 24 h later with anti-
ricin antibody were significantly improved by co-administration of
doxycycline. In contrast, co-administration of the
steroid drug
dexamethasone with anti-
ricin antibodies did not increase survival rates when administered at late hours after intoxication, however
dexamethasone did exert a positive effect on survival when applied in conjunction with the
doxycycline treatment. These studies strongly suggest that combined
therapy, comprised of neutralizing anti-
ricin antibodies and an appropriate
anti-inflammatory agent, can promote high-level protection against pulmonary ricinosis at clinically-relevant time points post-exposure.