Beta-adrenoceptor agonists block corticosteroid inhibition in eosinophils.
Although beta-adrenoceptor agonists are primary agents in therapy of asthma, epidemiological studies have suggested that frequent or prolonged used of these drugs could be associated with exacerbation of disease. Mechanisms of any adverse effects remain unclear although in vitro studies have suggested that beta-adrenoceptor agonists can block glucocorticoid actions. Because asthma is an inflammatory disease characterized by eosinophil infiltration of the airways, actions of beta-agonists and corticosteroids that alter eosinophil survival and mediator generation may be of importance. Eosinophil generation of superoxide anion, a potent mediator that can damage respiratory epithelium, was markedly increased after 2-24 h of in vitro beta-adrenoceptor agonist exposure. These proinflammatory effects are in contrast to inhibition of superoxide generation, which is observed with acute beta-agonist exposure. Corticosteroid treatment to reduce inflammation is combined with beta-agonist therapy in current asthma guidelines. Although dexamethasone independently decreased eosinophil superoxide anion generation, in the presence of beta-adrenoceptor agonist dexamethasone inhibition was minimal and not statistically significant. Eosinophil survival is a relevant factor to pulmonary inflammation. Although beta-adrenoceptor agonists did not independently increase eosinophil survival, glucocorticoid actions that increase apoptosis were blocked. Thus, in vitro beta-agonists can independently increase inflammatory mediator generation and block anti-inflammatory actions of corticosteroid.
Nielson
C P
CP
Immunopharmacology Research, Veterans Affairs Medical Center, Boise, Idaho 83702, USA. cnielson@micron.net
Hadjokas
N E
NE
D000319:Adrenergic beta-Antagonists / Q000009:adverse effects*; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D017209:Apoptosis; D001249:Asthma / Q000188:drug therapy* / Q000276:immunology*; D003907:Dexamethasone / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004336:Drug Antagonism; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D004804:Eosinophils / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D007249:Inflammation; D007958:Leukocyte Count; D016897:Respiratory Burst / Q000187:drug effects; D013481:Superoxides / Q000276:immunology
D000319:Adrenergic beta-Antagonists; D000893:Anti-Inflammatory Agents; D013481:Superoxides; D003907:Dexamethasone