COPD is characterized by inflammation of the airways, with increased numbers of activated macrophages, neutrophils and CD8+ T lymphocytes. Corti-costeroids are largely ineffective at suppressing this inflammatory process, prompting the search for new anti-inflammatory drugs. There are several approaches to inhibiting neutrophilic inflammation (Table 11.1).
PDEs break down cyclic nucleotides (cyclic adenosine monophosphate, cAMP and cyclic guanosine monophosphate, cGMP) which regulate cellular
Table 11.1 Inhibitors of neutrophilic inflammation.
• LTB4 antagonists (LY 29311, SC-53228, CP-105,696, SB 201146)
• Interleukin-8 inhibitors (IL-8 synthesis inhibitors, CXC receptor antagonists)
• Antioxidants (N-acetylcysteine, glutathione analogues, vitamins C and E, nitrones)
• TNF inhibitors (monoclonal antibodies, soluble receptors, TNF convertase inhibitors)
• Phosphodiesterase-4 inhibitors (SB 207499, CP 80633, CDP-840)
• NF-kB inhibitors (IkB kinase inhibitors, IkB-a gene transfer)
• Adhesion molecule inhibitors (anti CD11/CD18, anti-ICAM-1, E-selectin inhibitors)
• Prostaglandin E analogues (misoprostol, butaprost)
• Macrolide antibiotics (erythromycin, clarithromycin, roxithromycin)
ICAM-1, intercellular adhesion molecule-1; LTB4, leukotriene B4; NF-kB, nuclear factor-kB; TNF, tumour necrosis factor.
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