Dual role of Toll-like receptors in asthma and chronic obstructive pulmonary disease

Pharmacol Rev. 2012 Apr;64(2):337-58. doi: 10.1124/pr.111.004622. Epub 2012 Mar 8.

Abstract

During the last decade, significant research has been focused on Toll-like receptors (TLRs) in the pathogenesis of airway diseases. TLRs are pattern recognition receptors that play pivotal roles in the detection of and response to pathogens. Because of the involvement of TLRs in innate and adaptive immunity, these receptors are currently being exploited as possible targets for drug development. Asthma and chronic obstructive pulmonary disease (COPD) are chronic inflammatory airway diseases in which innate and adaptive immunity play an important role. To date, asthma is the most common chronic disease in children aged 5 years and older. COPD is prevalent amongst the elderly and is currently the fifth-leading cause of death worldwide with still-growing prevalence. Both of these inflammatory diseases result in shortness of breath, which is treated, often ineffectively, with bronchodilators and glucocorticosteroids. Symptomatic treatment approaches are similar for both diseases; however, the underlying immunological mechanisms differ greatly. There is a clear need for improved treatment specific for asthma and for COPD. This review provides an update on the role of TLRs in asthma and in COPD and discusses the merits and difficulties of targeting these proteins as novel treatment strategies for airway diseases. TLR agonist, TLR adjuvant, and TLR antagonist therapies could all be argued to be effective in airway disease management. Because of a possible dual role of TLRs in airway diseases with shared symptoms and risk factors but different immunological mechanisms, caution should be taken while designing pulmonary TLR-based therapies.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Age Factors
  • Aged
  • Animals
  • Asthma / drug therapy
  • Asthma / immunology*
  • Asthma / physiopathology
  • Child
  • Child, Preschool
  • Drug Delivery Systems
  • Drug Design
  • Humans
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Pulmonary Disease, Chronic Obstructive / immunology*
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Risk Factors
  • Toll-Like Receptors / agonists
  • Toll-Like Receptors / antagonists & inhibitors
  • Toll-Like Receptors / immunology*

Substances

  • Toll-Like Receptors