Cytokine Therapeutics for Asthma: An Appraisal of Current Evidence and Future Prospects

David      Alvarez; Ryan   E.   Wiley; Manel      Jordana

Abstract

Although current pharmacopoeia is effective in alleviating asthma symptomatology, it is equally unable to modify the fundamental immunological basis of the allergic diathesis. The explosion in knowledge of the immunobiology of cytokines that has occurred in the last decade has remarkably clarified our understanding of the pathogenesis of allergic asthma, and has unleashed a plethora of compelling opportunities. In the first part of this review, we will summarize current knowledge on the pathogenesis of allergic asthma, with particular emphasis on relevant cytokine networks. This will position us to appraise critically initiatives in the search to modulate cytokine targets that are key to the expression of the allergic asthma phenotype. We will review the use of recombinant cytokines, soluble cytokine receptors, cytokine receptor antagonists and cytokine inhibitors, in pre-clinical and clinical development. Finally, we will assess the applicability of transgene-based modalities, including anti-sense oligonucleotide technology and gene therapy, as novel therapeutic strategies in the treatment of allergic Asthma.

Keywords: Cytokine Therapeutics, Asthma, Recombinant cytokines, Cytokine receptors, VCAM-1, Pro-Inflammatory Cytokines, Th2-Associated Cytokines, Anti-Inflammatory Cytokines, Interferon, TRANSGENE-BASED MODALITIES