Comment in:

J Allergy Clin Immunol. 2006 Mar;117(3):712; author reply 712-3.

Modulation of GM-CSF release by enantiomers of beta-agonists in human airway smooth muscle.

Asthma, Allergy, and Airway Research Center, Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh Medical Center, PA 15213, USA. amerdesbt@upmc.edu

BACKGROUND: beta 2 -Adrenergic receptor agonists can reduce the release of GM-CSF by human airway smooth muscle cells (HASMCs). These effects are considered anti-inflammatory and are ascribed to the activity of the (R)-enantiomer within the racemate of the agonist. However, the effect of the (S)-enantiomer on GM-CSF release, once thought to be inert, has not been extensively explored. Objective We hypothesized that the (S)-enantiomer may counter the effects of the (R)-enantiomer, potentially increasing GM-CSF release. Therefore, the effects of administration of individual and combined enantiomers on GM-CSF release were examined. METHODS: Cultured HASMCs were stimulated with IL-1beta, TNF-alpha, and IFN-gamma and treated with (R)-enantiomers and (S)-enantiomers of albuterol and formoterol, with and without propranolol and ICI-118,551, and in combination with dexamethasone. GM-CSF in the resulting conditioned media was assessed by ELISA. RESULTS: (R)-enantiomers significantly reduced GM-CSF release by as much as 41% ( P < .05), which was reversible with propranolol. In contrast, (S)-enantiomers significantly increased GM-CSF release by as much as 34% ( P < .05) over release with no drug, and by 25% to 40% ( P < .05) when added with (R)-enantiomers. The decremental effect of dexamethasone was amplified by (R)-enantiomers but inhibited by (S)-enantiomers. Both propranolol and ICI-118,551 alone increased GM-CSF release in a concentration-dependent fashion, similar to (S)-enantiomers. CONCLUSION: We conclude that GM-CSF release by HASMC is downregulated by (R)-enantiomers and enhanced by (S)-enantiomers. The reversal of (R)-enantiomer and dexamethasone effects by the (S)-enantiomer suggests suppression of their anti-inflammatory effects, perhaps through an antagonistic mechanism similar to propranolol.

PMID: 15990776 [PubMed - indexed for MEDLINE]