Salbutamol modulates the balance of Th1 and Th2 cytokines by mononuclear cells from allergic asthmatics.
BACKGROUND
There is evidence that excessive use of inhalational beta(2)-agonists induces the deterioration of asthma. Although the exact mechanism of this remains to be elucidated, overuse of beta(2)-agonists may impair the Th1/Th2 balance in asthmatic airways. The aim of the present study was to evaluate whether salbutamol, a representative inhalational beta(2)-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-gamma, IL-13, TNF-alpha and RANTES in the cell supernatants were measured using ELISA.


RESULTS
In PBMCs from healthy volunteers, salbutamol did not modify IFN-gamma production, but increased the spontaneous production of IL-13. In contrast, salbutamol significantly inhibited the spontaneous and ionomycin- plus PMA-stimulated production of IFN-gamma 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-alpha. Finally, salbutamol enhanced the production of RANTES induced by Df allergen in asthmatics.


CONCLUSIONS
Salbutamol inhibits IFN-gamma 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.
Department of Respiratory Medicine, Saitama Medical University, Saitama, Japan.
Takefumi
T
Yamaguchi
Tomoyuki
T
Soma
Yotaro
Y
Takaku
Kazuyuki
K
Nakagome
Koichi
K
Hagiwara
Minoru
M
Kanazawa
Makoto
M
Nagata
D000328:Adult; D000420:Albuterol / Q000494:pharmacology*; D039741:Antigens, Dermatophagoides / Q000276:immunology / Q000494:pharmacology; D001249:Asthma / Q000276:immunology / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000378:metabolism; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015759:Ionomycin / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
D039741:Antigens, Dermatophagoides; D018946:Chemokine CCL5; D018793:Interleukin-13; D014409:Tumor Necrosis Factor-alpha; D015759:Ionomycin; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate; D000420:Albuterol