Advances in immunopharmacology of asthma

Citation
Wsf. Wong et Dsk. Koh, Advances in immunopharmacology of asthma, BIOCH PHARM, 59(11), 2000, pp. 1323-1335
Citations number
134
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOCHEMICAL PHARMACOLOGY
ISSN journal
00062952 → ACNP
Volume
59
Issue
11
Year of publication
2000
Pages
1323 - 1335
Database
ISI
SICI code
0006-2952(20000601)59:11<1323:AIIOA>2.0.ZU;2-D
Abstract
Asthma is a chronic inflammatory disease characterized by airway hyperrespo nsiveness 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 in terleukin (IL)-4 and IL-5 and their corresponding signaling pathways in the pathophysiology of the disease. These complex pathways may involve the act ivation of signal transducers and activators of transcription (STATs) and n uclear factor-kappa B (NF-kappa B). 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 inf lammation. An increase in the 3',5'-cyclic adenosine monophosphate (cAMP) l evel generally suppresses the activities of immune and inflammatory cells, and the level of cAMP is closely regulated by a family of phosphodiesterase s (PDEs). Heparin, a glycosaminoglycan released exclusively from mast cells , also is believed to possess anti-inflammatory actions. Many new therapeut ic agents have been developed either to attenuate the pro-inflammatory proc esses in asthma or to augment the host anti-inflammatory mechanisms. In thi s article, we discuss the immunopharmacology of several of these agents, wh ich include heparin and inhibitors of PDEs, tyrosine kinases, and NF-kappa B, as well as antibodies and soluble receptors directed against IgE, IL-4, and IL-5. BIOCHEM PHARMACOL 59;11:1323-1355, 2000. (C) 2000 Elsevier Scienc e Inc.