Agents against cytokine synthesis or receptors

Eur J Pharmacol. 2006 Mar 8;533(1-3):289-301. doi: 10.1016/j.ejphar.2005.12.046. Epub 2006 Feb 2.


Various cytokines play a critical role in pathophysiology of chronic inflammatory lung diseases including asthma and chronic obstructive pulmonary disease (COPD). The increasing evidence of the involvement of these cytokines in the development of airway inflammation raises the possibility that these cytokines may become the novel promising therapeutic targets. Studies concerning the inhibition of interleukin (IL)-4 have been discontinued despite promising early results in asthma. Although blocking antibody against IL-5 markedly reduces the infiltration of eosinophils in peripheral blood and airway, it does not seem to be effective in symptomatic asthma, while blocking IL-13 might be more effective. On the contrary, anti-inflammatory cytokines themselves such as IL-10, IL-12, IL-18, IL-23 and interferon-gamma may have a therapeutic potential. Inhibition of TNF-alpha may also be useful in severe asthma or COPD. Many chemokines are also involved in the inflammatory response of asthma and COPD through the recruitment of inflammatory cells. Several small molecule inhibitors of chemokine receptors are now in development for the treatment of asthma and COPD. Antibodies that block IL-8 reduce neutrophilic inflammation. Chemokine CC3 receptor antagonists, which block eosinophil chemotaxis, are now in clinical development for asthma therapy. As many cytokines are involved in the pathophysiology of inflammatory lung diseases, inhibitory agents of the synthesis of multiple cytokines may be more useful tools. Several such agents are now in clinical development.

Publication types

  • Review

MeSH terms

  • 3',5'-Cyclic-AMP Phosphodiesterases / antagonists & inhibitors
  • 3',5'-Cyclic-AMP Phosphodiesterases / metabolism
  • Animals
  • Anti-Asthmatic Agents / pharmacology*
  • Anti-Asthmatic Agents / therapeutic use
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use
  • Antibodies, Monoclonal, Humanized
  • Asthma / drug therapy*
  • Asthma / metabolism
  • Clinical Trials as Topic
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Cytokines / antagonists & inhibitors*
  • Cytokines / metabolism
  • Etanercept
  • Humans
  • Immunoglobulin G / pharmacology
  • Immunoglobulin G / therapeutic use
  • Interleukins / antagonists & inhibitors
  • Interleukins / metabolism
  • Phosphodiesterase Inhibitors / pharmacology
  • Phosphodiesterase Inhibitors / therapeutic use
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / enzymology
  • Receptors, Cytokine / antagonists & inhibitors*
  • Receptors, Cytokine / metabolism
  • Receptors, Tumor Necrosis Factor / therapeutic use
  • Respiratory System / drug effects
  • Respiratory System / metabolism
  • Signal Transduction / drug effects
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism


  • Anti-Asthmatic Agents
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Cytokines
  • Immunoglobulin G
  • Interleukins
  • Phosphodiesterase Inhibitors
  • Receptors, Cytokine
  • Receptors, Tumor Necrosis Factor
  • Tumor Necrosis Factor-alpha
  • mepolizumab
  • 3',5'-Cyclic-AMP Phosphodiesterases
  • Cyclic Nucleotide Phosphodiesterases, Type 4
  • Etanercept