Effects of antiasthmatic agents on the functions of peripheral blood monocyte-derived dendritic cells from atopic patients.
BACKGROUND
Dendritic cells (DCs), the antigen-presenting cells in the airway, play a critical role in asthma. Nevertheless, there is little information on the effects of antiasthmatic agents on DCs.


OBJECTIVE
The purpose of the present study was to determine the effects of representative antiasthmatic agents, including cysteinyl leukotriene (cysLT) 1 receptor antagonists, corticosteroid, and tacrolimus, on DCs in inducing allergy.


METHODS
Human peripheral blood monocyte-derived DCs (MoDCs) generated from atopic and healthy subjects were pulsed with Dermatophagoides farinae allergen in the presence of medium alone, pranlukast, montelukast, dexamethasone, or tacrolimus. The mRNA expressions of cysLT receptor, cysLTs producing enzymes, and various surface markers on MoDCs, as well as the concentrations of cysLTs, IL-10, and IL-12 in cultured supernatants, were determined. MoDCs were also cocultured in vitro with autologous CD4(+) T cells, and IL-5 and IFN-gamma production was measured.


RESULTS
MoDCs of atopic patients expressed mRNAs of cysLT1 receptor and cysLT-producing enzymes, and allergen pulsing significantly increased cysLT production. MoDCs of atopic patients showed a T(H)2-favoring phenotype and induced T(H)2-skewed cytokine production from autologous CD4(+) T cells. Dexamethasone and tacrolimus inhibited allergen-pulsed MoDC-induced cytokine production by autologous CD4(+) T cells without and with IL-10 inhibition, respectively. CysLT1 receptor antagonists had no effect on MoDC functions.


CONCLUSIONS
Our results indicate that MoDCs of atopic patients induce a T(H)2 reaction. Corticosteroid and tacrolimus, but not cysLT1 receptor antagonists, inhibit T(H)2 reactions, and this effect is probably mediated through different pathways.
Saeki
Sachiko
S
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852-8501, Japan.
Matsuse
Hiroto
H
Kondo
Yuki
Y
Machida
Ikuko
I
Kawano
Tetsuya
T
Tomari
Shinya
S
Obase
Yasushi
Y
Fukushima
Chizu
C
Kohno
Shigeru
S
D000305:Adrenal Cortex Hormones / Q000008:administration & dosage / Q000494:pharmacology; D000328:Adult; D018927:Anti-Asthmatic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D039741:Antigens, Dermatophagoides / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation; D003545:Cysteine / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects*; D005260:Female; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000188:drug therapy* / Q000276:immunology; D020024:Leukotriene Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D009000:Monocytes / Q000166:cytology*; D016559:Tacrolimus / Q000008:administration & dosage / Q000494:pharmacology
D000305:Adrenal Cortex Hormones; D018927:Anti-Asthmatic Agents; D039741:Antigens, Dermatophagoides; D016207:Cytokines; D020024:Leukotriene Antagonists; D015289:Leukotrienes; C112381:cysteinyl-leukotriene; D003545:Cysteine; D016559:Tacrolimus