Regulation of mast cells by beta-agonists.
The human lung mast cell is known to be a critical effector cell in the mediation of asthma. Activation of the mast cell by allergens and other stimuli leads to the release and generation of a wide variety of autacoids that cause bronchoconstriction, promote inflammation, and may influence airway remodeling. Therefore, the stabilization of mast cells has obvious value in the prevention of asthma. Among the drugs used to treat asthma, only beta-agonists are effective stabilizers of mast cells. Both short- and long-acting beta-agonists are effective against mast cells, but there are differences between agonists regarding the extent of inhibitory activity attained. Consequently, the type of beta-agonist prescribed influences the degree of mast cell stabilization possible. Despite the potential value of attenuating mast cell activity with beta-agonists, this benefit may diminish with time because of the development of tolerance. Both short- and long-acting beta-agonists can induce tolerance to mast cell stabilization, and generally, higher efficacy agonists tend to induce greater levels of tolerance; however, weaker agonists induce greater levels of tolerance than might be expected. Tolerance to the mast-cell-stabilizing effects of beta- agonists may be an issue clinically, because this occurs more readily than tolerance to smooth muscle relaxation. This could lead to a situation in which beta-agonists fail to prevent the release of mediators from mast cells but can still effectively relax airway smooth muscle. The continued ability to bronchodilate could mask the unfavorable consequences of unchecked mediator release from mast cells.
Peachell
Peter
P
Academic Unit of Clinical Pharmacology, University of Sheffield, Royal Hallamshire Hospital, Sheffield, United Kindgom. p.t.peachell@shef.ac.uk
D000318:Adrenergic beta-Agonists / Q000494:pharmacology* / Q000627:therapeutic use; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D004361:Drug Tolerance; D006801:Humans; D008407:Mast Cells / Q000187:drug effects / Q000502:physiology*
D000318:Adrenergic beta-Agonists