Glucocorticosteroids are widely used in the treatment of
asthma and
chronic obstructive pulmonary disease (
COPD). However, there are growing concerns about the side effect profile of this class of drug, particularly an increased risk of
pneumonia. Over the last two decades there have been many attempts to find drugs to allow a reduction of glucocorticosteroids, including
xanthines such as
theophylline. Use of
xanthines has been shown to lead to a reduction in the requirement for glucocorticosteroids, although
xanthines also have a narrow therapeutic window limiting their wider use.
Doxofylline is another
xanthine that has been shown to be of clinical benefit in patients with
asthma or
COPD, but to have a wider therapeutic window than
theophylline. In the present study we have demonstrated that
doxofylline produces a clear
steroid sparing effect in both an allergic and a non-allergic model of
lung inflammation. Thus, we have shown that concomitant treatment with a low dose of
doxofylline and a low dose of the glucocorticosteroid
dexamethasone (that alone had no effect) significantly reduced both
allergen-induced eosinophil infiltration into the lungs of allergic mice, and
lipopolysaccharide (LPS)-induced neutrophil infiltration into the lung, equivalent to a higher dose of each drug. Our results suggest that
doxofylline demonstrates significant anti-inflammatory activity in the lung which can result in significant
steroid sparing activity.