Theophylline is a nonspecific phosphodiesterase (PDE) inhibitor, adenosine receptor antagonist, and histone deacetylase (HDAC) activator. Theophylline promotes bronchodilation by inhibiting PDE3, thereby treating respiratory diseases; and exerts anti-inflammatory effects by inhibiting PDE4 and the activation of HDAC-2, reversing corticosteroid resistance, for the treatment of asthma and chronic obstructive pulmonary disease (COPD)[1].
In vitro, Theophylline (20, 100, and 500µM; 2h) inhibited IκBα protein degradation, NF-κB activation, and the production of pro-inflammatory cytokines in A549 cells in a concentration-dependent manner[2]. Theophylline (10μg/mL; 24h) reduced the level of the anti-apoptotic protein Bcl-2 and induced apoptosis in eosinophils[3].
In vivo, treatment with Theophylline (100mg/kg; i.p.), followed 30min later by an LPS challenge (20mg/kg; i.p.), significantly blunted the LPS-induced increase in nitrite/nitrate levels in the plasma of mice[3]. Treatment with Theophylline (100mg/kg; i.p.), followed 30min later by an LPS challenge (5mg/kg; i.p.) enhanced LPS-induced plasma IL-6 and IL-10 levels in mice during the whole response[3].
References:
[1] Barnes, Peter J. “Theophylline.” American journal of respiratory and critical care medicine vol. 188,8 (2013): 901-6.
[2] Ichiyama, T et al. “Theophylline inhibits NF-kappa B activation and I kappa B alpha degradation in human pulmonary epithelial cells.” Naunyn-Schmiedeberg's archives of pharmacology vol. 364,6 (2001): 558-61.
[3] Németh, Z H et al. “Amrinone and theophylline differentially regulate cytokine and nitric oxide production in endotoxemic mice.” Shock (Augusta, Ga.) vol. 7,5 (1997): 371-5.