Discovery Of A New Mechanism To Control Allergic Asthma Using Fullerene C70 Derivatives

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We have shown previously that fullerene derivatives (FD) can stabilize mast cells (MC) in vitro and in vivo. Here, we examine their in vivo therapeutic effect on asthma, a MC driven disease. We used Ova-challenge, MC-dependent and independent models. Asthma was induced in mice and animals were treated intranasally (i.n.) with or without FD either simultaneously with treatment or following induction of pathogenesis. Several parameters indicative of disease were measured including lung function, cellular infiltration, and inflammatory mediators. We find that FD-treated mice have significantly reduced airway inflammation, eosinophilia, and bronchoconstriction. Fullerene treatments are effective even when given after disease is established, suggesting that these compounds may have therapeutic potential in treating human disease. Interestingly, we report a novel inhibitory mechanism as FD stimulate the production of cis-epoxyeicosatrienoic acid (EET), an anti-inflammatory P-450 eicosanoid metabolite, in the lung. Using the same in vivo models, it is shown that two inhibitors of EET's reverse the inhibition seen in FD treated mice. The inhibitory capabilities of the EET's induced by FD reported here represent a new therapeutic strategy for asthma interventions through either using agents that induce the EET's or perhaps by inhalation of the EET's themselves.