Pranlukast, a cysteinyl leukotriene receptor 1 antagonist, attenuates allergen-specific tumour necrosis factor alpha production and nuclear factor kappa B nuclear translocation in peripheral blood monocytes from atopic asthmatics.
BACKGROUND
The cysteinyl leukotriene receptor 1 (cysLTR1) antagonists are useful for oral treatment of bronchial asthma. The underlying mechanism of cysLTR1 antagonists on inhibition of inflammatory cytokine production is yet to be determined.


OBJECTIVE
The present study was designed to determine the effect of pranlukast, a cysLTR1 antagonist, on production of inflammatory cytokines by allergen-stimulated peripheral blood monocytes (PBM) from atopic asthmatics.


METHODS
PBM were obtained from normal control (n = 10) and Dermatophagoides farinae (Der f) allergen-sensitized atopic asthmatics (n = 12), and were cultured in the presence of Der f allergen. The production of TNF-alpha and nuclear-translocation of nuclear factor kappa B (NF-kappa B) was determined. In atopic asthmatics, pranlukast, tacrolimus or dexamethasone was added before stimulation by Der f. The additive effect of pranlukast and dexamethasone was also determined.


RESULTS
PBM from atopic asthmatics cultured with Der f exhibited a significant increase in TNF-alpha production and nuclear translocation of NF-kappa B compared with normal control (P < 0.01). Pranlukast, tacrolimus and dexamethasone significantly inhibited production of TNF-alpha and nuclear-translocation of NF-kappa B in PBM of atopic asthmatics (P < 0.01). An additive effect of pranlukast on low-dose dexamethasone was also demonstrated. However, LTD4 did not induce TNF-alpha production or NF-kappa B nuclear translocation.


CONCLUSIONS
Our results suggest that pranlukast may inhibit TNF-alpha production via suppression of NF-kappa B activation through pathways distinct from cysLTR1 antagonism.
Tomari
S
S
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Matsuse
H
H
Machida
I
I
Kondo
Y
Y
Kawano
T
T
Obase
Y
Y
Fukushima
C
C
Shimoda
T
T
Kohno
S
S
D000328:Adult; D000485:Allergens / Q000494:pharmacology; D039741:Antigens, Dermatophagoides / Q000276:immunology; D060829:Arthropod Proteins; D001249:Asthma / Q000276:immunology*; D002478:Cells, Cultured; D002867:Chromones / Q000494:pharmacology*; D003546:Cysteine Endopeptidases; D016207:Cytokines / Q000096:biosynthesis*; D040001:Dermatophagoides farinae / Q000276:immunology; D003907:Dexamethasone / Q000494:pharmacology; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D007963:Leukocytes, Mononuclear / Q000187:drug effects / Q000276:immunology*; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D008297:Male; D016328:NF-kappa B / Q000235:genetics; D016559:Tacrolimus / Q000494:pharmacology; D014178:Translocation, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000485:Allergens; D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D002867:Chromones; D016207:Cytokines; D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D020024:Leukotriene Antagonists; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D003546:Cysteine Endopeptidases; C451159:Dermatophagoides farinae antigen f 1; C047681:pranlukast; D016559:Tacrolimus