Advances in immunopharmacology of asthma

Abstract

Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness and recurrent reversible airway obstruction. As there appears to be a preponderance of T-helper 2 (Th2) cells over Th1 cells in asthma, more attention has been focused on the role of Th2-derived cytokines such as interleukin (IL)-4 and IL-5 and their corresponding signaling pathways in the pathophysiology of the disease. These complex pathways may involve the activation of signal transducers and activators of transcription (STATs) and nuclear factor-κB (NF-κB). On the other hand, immunoglobulin (Ig) E-mediated mechanisms and the protein tyrosine kinase signaling cascade are important in triggering the release of mediators from inflammatory cells. In spite of all of these, host regulatory mechanisms exist to limit the inflammation. An increase in the 3',5'-cyclic adenosine monophosphate (cAMP) level generally suppresses the activities of immune and inflammatory cells, and the level of cAMP is closely regulated by a family of phosphodiesterases (PDEs). Heparin, a glycosaminoglycan released exclusively from mast cells, also is believed to possess anti-inflammatory actions. Many new therapeutic agents have been developed either to attenuate the pro-inflammatory processes in asthma or to augment the host anti-inflammatory mechanisms. In this article, we discuss the immunopharmacology of several of these agents, which include heparin and inhibitors of PDEs, tyrosine kinases, and NF-κB, as well as antibodies and soluble receptors directed against IgE, IL-4, and IL-5. (C) 2000 Elsevier Science Inc.