Salbutamol Modulates the Balance of Th1 and Th2 Cytokines by Mononuclear Cells from Allergic Asthmatics

Abstract

Background: There is evidence that excessive use of inhalational β₂-agonists induces the deterioration of asthma. Although the exact mechanism of this remains to be elucidated, overuse of β₂-agonists may impair the Th1/Th2 balance in asthmatic airways. The aim of the present study was to evaluate whether salbutamol, a representative inhalational β₂-agonist, modifies the production of Th1- and Th2-type cytokines by mononuclear cells separated from patients with asthma and healthy volunteers. Methods: Peripheral blood mononuclear cells (PBMCs) obtained from 8 healthy volunteers and 10 patients with mild persistent asthma allergic to house dust mites were treated with either salbutamol or medium alone. PBMCs were then stimulated with either medium alone, house dust mite (Dermatophagoides farina, Df) allergen or a combination of ionomycin plus phorbol 12-myristate 13-acetate ester (PMA). Concentrations of IFN-γ, IL-13, TNF-α and RANTES in the cell supernatants were measured using ELISA. Results: In PBMCs from healthy volunteers, salbutamol did not modify IFN-γ production, but increased the spontaneous production of IL-13. In contrast, salbutamol significantly inhibited the spontaneous and ionomycin- plus PMA-stimulated production of IFN-γ by PBMCs from asthmatics. Salbutamol significantly enhanced both spontaneous and Df-induced production of IL-13 by PBMCs from asthmatics. Salbutamol did not modify the production of TNF-α. Finally, salbutamol enhanced the production of RANTES induced by Df allergen in asthmatics. Conclusions: Salbutamol inhibits IFN-γ and enhances IL-13 production by PBMCs from asthmatics. These effects would promote a Th1/Th2 imbalance in the airways and may therefore contribute to the deterioration of asthma.

(R)-Salbutamol Improves Imiquimod-Induced Psoriasis-Like Skin Dermatitis by Regulating the Th17/Tregs Balance and Glycerophospholipid Metabolism

“…These results are not in agreement with reports in which treatment of racemic salbutamol regulates the balance between Th1 and Th2 cytokines instead of Th17 and Treg [46]. Additionally, Dex markedly reduces the levels of IL-17 in mice plasma ( Figure 4D) and neutrophils ( Figure 4C) in mice blood, suggesting dexamethasone alleviates psoriasis by reducing the production of IL-17 from neutrophils rather than from Th17 cells [46]. However, the inhibition effects of Dexamethasone on total WBC, neutrophil, and monocyte in blood were much more less significant in comparing (R)-salbutamol in IMQ induced Psoriasis mice.…”

“…Collectively, these findings indicated that (R)-salbutamol attenuates psoriasis-like skin dermatitis induced by IMQ by regulating Th17 and Treg differentiation and inhibiting cytokines secretion. These results are not in agreement with reports in which treatment of racemic salbutamol regulates the balance between Th1 and Th2 cytokines instead of Th17 and Treg [46]. Additionally, Dex markedly reduces the levels of IL-17 in mice plasma ( Figure 4D) and neutrophils ( Figure 4C) in mice blood, suggesting dexamethasone alleviates psoriasis by reducing the production of IL-17 from neutrophils rather than from Th17 cells [46].…”

T cell responses to der f2 mite allergens in Thai allergic patients

“…Investigations of allergen-simulated release of IFN- from PBMC have produced mixed results. Some studies found decreased IFN- production in subjects with atopic diseases relative to healthy control subjects [14,30,31], whereas other studies reported no difference [32,33]. In our study, there was no significant difference in recombinant Der f2-stimulated IFN- production between allergic patients and control subjects, while we found that degree of Df-total extract-stimulated IFN- production was higher in allergic patients than in the control subjects.…”

Relationship of Adipokines with Immune Response and Lung Function in Obese Asthmatic and Non-Asthmatic Women

“…The correlation of serum adipokines and inflammatory markers from PBMC does not establish cause and effect, but suggest that serum adipokines may act through effector cells to alter the phenotype of airway inflammation in the obese. In addition, while PBMCs are readily available and well-described surrogates, they are not in fact airway inflammatory cells (27–31). Finally intrinsic factors such as circadian rhythmic release and reproductive hormone levels may alter circulating levels of leptin and adiponectin and these variables were not controlled for in our data collection.…”