LTB4 antagonism

LTB4 is one of the most important mediators for neutrophil granulocyte surv ival, trafficking and activation. A major role has been proposed in the pat hophysiology of respiratory diseases characterized by a neutrophilic-type o f inflammation, such as chronic bronchitis, severe asthma and cystic fibros is. Elevated LTB4 levels have been found in sputum and BAL fluid of patient s with COPD, cystic fibrosis and severe asthma. This constitutes the medica l rationale for testing LTB4 antagonists in certain forms of asthma and in COPD. A first clinical trial has demonstrated that an LTB4 antagonist could reduce the number of BAL fluid neutrophils in patients with mild asthma. S everal LTB4 antagonists are known, the most important ones being CP 195543, SC 53228, CGS 25019C, ONO 4057, LY 293111 Na, and BIIL 284 BS. All these c ompounds are specific LTB4 antagonists, but they differ with respect to eff icacy and pharmacokinetic properties. Their clinical evaluation is ongoing.