Targeting airway inflammation: novel therapies for the treatment of asthma.
It is now widely accepted that airway inflammation is the key factor underlying the pathogenesis of asthma. Inhaled corticosteroids remain the most important anti-inflammatory treatment for asthma. However, they are rather non-specific in their actions and their use raises concerns over side effects and compliance issues, particularly in children and adolescents. Moreover, a significant sub-group of asthmatic patients responds poorly or not at all to high-dose inhaled or systemic steroid treatment. Therefore, much effort is being made to develop novel more specific and safer therapy for asthma. Significant areas of drug development include humanised monoclonal antibodies (mAb) for asthma therapy including those against IL-4, IL-5, TNF and IL-13. Asthma-relevant cytokines or chemokines have been targeted in a number of other ways. These include: (1) the use of humanised blocking mAb to their receptors; (2) removal of cytokines or chemokines via binding to soluble receptors or small molecule receptor antagonists; and (3) drugs that block the signal transduction pathways activated following the interaction of cytokines or chemokines with their receptors. Another approach is to use anti-inflammatory cytokines directly or encourage their production thereby suppressing the allergic inflammatory process; these chemokines include IL-10, IL-12 and IFN-gamma. Finally, a further promising area involves targeting the allergic portion of the asthma phenotype using humanised anti-IgE mAb. This review will discuss the current status, therapeutic potential and potential problems of these novel drug developments in asthma therapy.
Walsh
Garry M
GM
School of Medicine, Institute of Medical Sciences, University of Aberdeen, Foresterhill, Aberdeen, UK. g.m.walsh@abdn.ac.uk
D018927:Anti-Asthmatic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001249:Asthma / Q000188:drug therapy* / Q000473:pathology; D018925:Chemokines / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000627:therapeutic use; D015195:Drug Design; D004358:Drug Therapy / Q000639:trends; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy / Q000473:pathology; D012137:Respiratory System / Q000187:drug effects* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology
D018927:Anti-Asthmatic Agents; D018925:Chemokines; D016207:Cytokines