Therapeutic activities of theophylline in chronic obstructive pulmonary disease.
Recent observations in asthmatics demonstrated anti-inflammatory and immunomodulatory activities of theophylline besides the bronchodilating effect. Theophylline inhibits the mediator release from mast cells, peripheral blood monocytes and alveolar macrophages. The proliferative response of T-cells as well as the influx of eosinophils in BAL fluid is inhibited by treatment with theophylline. The production and release of pro-inflammatory cytokines are affected by theophylline showing a potent inhibitory effect on the production of IL-1beta, TNF-alpha and IFN-gamma. The production of the anti-inflammatory cytokine IL-10 is increased. Evidence is mounting that the anti-inflammatory effects and immunomodulating actions are exerted at lower plasma concentrations than those required for bronchodilation. These activities are of relevance in the treatment of chronic obstructive pulmonary disease (COPD), a disease in which the inflammatory component is considered to be more important than previously thought.
Department of Respiratory Diseases, University Hospital, Ghent, Belgium.
R A
RA
Peleman
J C
JC
Kips
R A
RA
Pauwels
D000276:Adjuvants, Immunologic / Q000494:pharmacology / Q000627:therapeutic use; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use; D001993:Bronchodilator Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000037:antagonists & inhibitors; D007375:Interleukin-1 / Q000037:antagonists & inhibitors; D016753:Interleukin-10 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008173:Lung Diseases, Obstructive / Q000188:drug therapy*; D016676:Macrophages, Alveolar / Q000187:drug effects; D008407:Mast Cells / Q000187:drug effects; D013806:Theophylline / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors
D000276:Adjuvants, Immunologic; D000893:Anti-Inflammatory Agents; D001993:Bronchodilator Agents; D016207:Cytokines; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007371:Interferon-gamma; D013806:Theophylline