Arachidonic acid (AA) and
docosahexaenoic acid (DHA) play important roles in
inflammation and
disease progression, where AA is viewed as proinflammatory and
DHA as antiinflammatory. We observe in our model of allergic
asthma that the AA/DHA ratio is significantly skewed in a proinflammatory direction.
Fenretinide, a
vitamin A derivative, has been shown to correct
fatty acid imbalances in other diseases. Therefore, we explored if
fenretinide can have a protective effect in allergic
asthma. To accomplish this, we measured the levels of AA and DHA in the lungs of nonallergic,
ovalbumin-induced allergic, and
fenretinide-treated allergic mice. We also investigated the effect of allergic
asthma and
fenretinide treatment on markers of oxidative stress, levels of metabolites,
IgE production,
airway hyperresponsiveness, and histological changes. Our data demonstrate that treatment of
allergen-sensitized mice with
fenretinide before
allergen challenge prevents
ovalbumin-induced changes in the AA/DHA ratio. The levels of several metabolites, such as
serotonin, and markers of cellular stress, which are increased after
ovalbumin challenge, are also controlled by
fenretinide treatment. We observed the protective effect of
fenretinide against
ovalbumin-induced
airway hyperresponsiveness and
inflammation in the lungs, illustrated by a complete block in the infiltration of inflammatory cells to the airways and dramatically diminished goblet cell proliferation, even though
IgE remained high. Our results demonstrate that
fenretinide is an effective agent targeting
inflammation, oxidation, and lung pathology observed in allergic
asthma.