摘要：

Background:β 2-Adrenergic agonists interact with specific receptors on T lymphocytes to mediate anti-inflammatory activities. However, anti-inflammatory effects are not observed when β 2-adrenergic agonists are administered in vivo as racemates. Objective: We hypothesized that anti-inflammatory influences are mediated by the (R)-isomer and are masked in the additional presence of the (S)-isomer. Methods: Antigen-specific T-cell lines were generated in the presence of recombinant human IL-2 and tetanus with or without varying concentrations of (R)- and (S)-isomers of albuterol alone or in combination. Parallel lines were generated in the presence of propranolol. Cells were briefly pulsed with PHA and evaluated for proliferation, apoptosis, and cytokine secretion. Results: (R)-Albuterol significantly inhibited T-cell proliferation (77.0% ± 9.7% of control at 10 8 mol/L and 61.1% ± 9.0% at 10 7 mol/L). No influence was observed with (S)-albuterol alone. However, the addition of (S)-albuterol to (R)-albuterol mediated a dose-dependent increase in proliferation. At equivalent concentrations of the 2 isomers, proliferation was unchanged from the control, whereas at 10 6 mol/L (S)-albuterol, proliferation was enhanced. Both the inhibitory effects of (R)-albuterol alone and the stimulating influence of (R)- plus (S)-albuterol were blocked in the additional presence of propranolol. (R)-Albuterol at 10 8 mol/L inhibited IL-2 and IFN-γ production. Racemic albuterol (10 8 mol/L each) had no influence on cytokine production; however, the combination of 10 8 mol/L (R)-albuterol with 10 6 (S)-albuterol stimulated production of IL-2 and IL-13. No effects were observed on apoptosis or cell viability. Conclusion: These studies confirm the β-adrenergic receptor-specific anti-inflammatory effects of (R)-albuterol. The racemate had minimal influences on proliferation or cytokine production. The presence of excess (S)-albuterol resulted in proinflammatory influences. We hypothesize that the (S)-isomer functions as an inverse agonist to switch the function of the β 2-adrenergic receptor. (J Allergy Clin Immunol 2002;109:449-54.)

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