HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Barnes, P.J. Search for Related Content PubMed PubMed Citation Articles by Barnes, P.J.

Cytokine modulators as novel therapies for airway disease

CORRESPONDENCE: P.J. Barnes, Dept of Thoracic Medicine, National Heart & Lung Institute, Imperial College, Dovehouse Street, London, SW3 6LY, UK. Fax: 0207 3515675

Keywords: chemokine receptor, cytokine, interleukin-4, interleukin-5, interleukin-9, interleukin-10

Received: March 26, 2001
Accepted April 25, 2001

Cytokines play a critical role in orchestrating and perpetuating inflammation in asthma and chronic obstructive pulmonary disease (COPD), and several specific cytokine and chemokine inhibitors are now in development for the future therapy of these diseases.

Anti-interleukin (IL)-5 is very effective at reducing peripheral blood and airway eosinophil numbers, but does not appear to be effective against symptomatic asthma. Inhibition of IL-4 with soluble IL-4 receptors has shown promising early results in asthma. Inhibitory cytokines, such as IL-10, interferons and IL-12 are less promising, as systemic delivery causes side-effects. Inhibition of tumour necrosis factor- may be useful in severe asthma and for treating severe COPD with systemic features.

Many chemokines are involved in the inflammatory response of asthma and COPD and several low-molecular-weight inhibitors of chemokine receptors are in development. CCR3 antagonists (which block eosinophil chemotaxis) and CXCR2 antagonists (which block neutrophil and monocyte chemotaxis) are in clinical development for the treatment of asthma and COPD respectively.

Because so many cytokines are involved in asthma, drugs that inhibit the synthesis of multiple cytokines may prove to be more useful; several such classes of drug are now in clinical development and any risk of side-effects with these nonspecific inhibitors may be reduced by the use of inhalational route of delivery.