Theophylline (TPL)

Theophylline is a methylxanthine drug used in therapy for respiratory diseases such as COPD and asthma under a variety of brand names. As a member of the xanthine family, it bears structural and pharmacological similarity to caffeine. It has been shown that theophylline may reverse the clinical observations of steroid insensitivity in patients with COPD and asthmatics that are active smokers (a condition resulting in oxidative stress) via a distinctly separate mechanism. Theophylline in vitro can restore the reduced HDAC (histone deacetylase) activity that is induced by oxidative stress, returning steroid responsiveness toward normal. Furthermore, theophylline has been shown to directly activate HDAC2. Corticosteroids switch off the inflammatory response by blocking the expression of inflammatory mediators through deacetylation of histones, an effect mediated via histone deacetylase-2 (HDAC2).