(S)-Albuterol Increases the Production of Histamine and IL-4 in Mast Cells

Abstract

Background: Racemic albuterol is an equimolar mixture of (R)-albuterol and (S)-albuterol. Previous studies indicated that (S)-albuterol may exert proinflammatory effects. We investigated the effect of (S)-albuterol in the production of mast cell mediators such as histamine and interleukin (IL)-4. Methods: Murine mast cells were either unstimulated or stimulated by IgE-receptor crosslinking. Both groups of mast cells were pretreated with either (R)- or (S)-albuterol. Histamine release and IL-4 secretion were measured by ELISA. Expression of L-histidine decarboxylase (L-HDC) and IL-4 was analyzed by semiquantitative reverse transcription-polymerase chain re- action. Results: In the overnight IgE-stimulated group, secreted histamine and total histamine were approximately 19.9 and 18.3% greater in cells co-treated with (S)-albuterol than untreated cells, respectively (n = 4, p < 0.002, p < 0.02), whereas there was no significant difference between the cells treated with (R)-albuterol and untreated cells. When the IgE-stimulated cells were treated with (S)-albuterol for 6 and 24 h, histamine release was approximately 18.3 and 24% greater, respectively (n = 4, p < 0.01). L-HDC is an essential enzyme for synthesizing histamine and its message was significantly induced in mast cells treated with (S)-albuterol. Both IL-4 message and protein were also significantly increased after treatment with (S)-albuterol. In the overnight IgE-stimulated group, IL-4 secretion was increased by approximately 58.8% upon exposure to (S)-albuterol (n = 5, p < 0.01). (R)-albuterol had no effect on mast cell mediator release. Conclusion: (S)-albuterol may have adverse effects in asthma control by activating mast cells to produce inflammatory mediators such as histamine and IL-4.