Targeting eosinophils in asthma: current and future state of cytokine- and chemokine-directed monoclonal therapy.

摘要

Asthma pathology includes reversible airway obstruction, airway hyperresponsive-ness (AHR) to normally harmless stimuli, and airway inflammation characterized by infiltration of the airways by activated lymphocytes and eosinophils. Eosinophils are not present in healthy lungs in significant numbers; however, in asthma patients their numbers in blood, sputum and lung tissue correlate with disease severity. Eosinophils contain cytotoxic cationic granule proteins, including major basic protein, eosinophil cationic protein, eosinophil-derived neurotoxin and eosinophil peroxidase. Eosinophils can also synthesize up to 28 cytokines, chemo-kines and growth factors and are potent sources of the membrane-derived lipid mediators leukotriene C4 and platelet-activating factor. The latter two mediators are potent stimulants of mucus secretion and of smooth muscle contraction, thereby making a significant contribution to airway obstruction and narrowing.