Title:Inflammation and Muscle Weakness in COPD: Considering a Renewed Role for Theophylline?
VOLUME: 14 ISSUE: 1
Author(s):Stephen Allen*, Ahmed Khattab, Michael Vassallo and Joseph Kwan
Affiliation:Bournemouth University, Poole, Bournemouth University, Poole, Bournemouth University, Poole, The University of Hong Kong, Hong Kong SAR
Keywords:Chronic obstructive pulmonary disease, illness behaviour, immune modulation, pulmonary rehabilitation,
sarcopenia, systemic inflammation, theophylline.
Abstract:Background: The methyl-xanthine drug theophylline has been used for the treatment of
asthma and chronic obstructive pulmonary disease (COPD) for several decades. Phosphodiesterase
inhibition leading to smooth muscle relaxation is its main mode of action as a broncho-dilating agent,
requiring blood theophylline concentrations close to the toxic range and a consequent problem with
side effects. It also has anti-inflammatory effects that occur at relatively low concentrations.
Objective: To explore supporting evidence for how other properties of theophylline could be of
considerable clinical utility, particularly in reducing weakness and overt sarcopenia, based on its antiinflammatory,
steroid-sparing and immune-modulating properties.
Methods: PUBMED and MEDLINE were scanned using the search terms: theophylline, antiinflammatory,
cytokine, inflammation, ageing, sarcopenia, frailty, chronic obstructive airways
disease, pulmonary rehabilitation. High quality articles were selected, read in-depth and discussed by
the authors, then used as the basis for a proposition on the potential anti-inflammatory and antisarcopenic
use of theophylline.
Findings: The anti-inflammatory properties of theophylline are mainly mediated by histone
deacetylase induction in immune competent cells with a resulting shift toward the expression of a less
inflamed phenotype, including a reduction of the release of pro-inflammatory cytokines and the
associated increase in anti-inflammatory cytokines. These effects occur at blood theophylline
concentrations well below the range for direct broncho-dilatation.
Conclusion: There are potential therapeutic benefits of theophylline that are systemic and not
confined to airways inflammation in COPD. There is scope for a beneficial effect in other chronic
inflammatory states and post-acute inflammation with slow resolution. There is compelling evidence
that theophylline could be used for anti-inflammatory adjunctive treatment to improve independent
function, muscle strength and other outcomes in individuals recovering from acute inflammatory
episodes, including but not limited to exacerbations of COPD, and as a pharmaceutical intervention in
support of pulmonary rehabilitation.
