Steroids may prevent or reverse the desensitization occurring with prolonged exposure to short-acting β2-adrenergic receptor agonists in treating chronic obstructive pulmonary disease and asthma.
Phillip R. Cooper, Ph.D., and Dr. Reynold A. Panettieri Jr. incubated slices of human lung tissue containing small airways with the short-acting β2-adrenergic receptor agonist albuterol for 3, 6, or 12 hours at different concentrations. The incubation weakened subsequent isoproterenol-induced relaxation in a dose- and time-dependent manner (J. Allergy Clin. Immunol. 2008 Sept. 9 [doi: 10.1016/j.jaci.2 008.07. 040]).
After 12 hours of albuterol incubation, they noted a 40% decrease in maximum relaxation and a 45% decrease in airway sensitivity, compared with control values. The differences were statistically significant. In contrast, preincubating the slices of lung tissue with dexamethasone for 1 hour prevented the albuterol-induced desensitization. A 30-minute dexamethasone incubation didn't change albuterol-induced desensitization.
This is the first study to demonstrate a model of β2-adrenergic receptor tolerance in human small airways. It provides a platform to determine the exact mechanisms of β-agonist desensitization in humans, as well as ways of preventing tolerance to those agonists in human airway disease. The take-home message is that steroids can reverse that tolerance, said the authors. They said they had no conflicts of interest.