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Clinical & Experimental Allergy

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

Authors


Hiroto Matsuse. E-mail: hmatsuse@net.nagasaki-u.ac.jp

Summary

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-α and nuclear-translocation of nuclear factor kappa B (NF-κB) 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-α production and nuclear translocation of NF-κB compared with normal control (P < 0.01). Pranlukast, tacrolimus and dexamethasone significantly inhibited production of TNF-α and nuclear-translocation of NF-κB 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-α production or NF-κB nuclear translocation.

Conclusion Our results suggest that pranlukast may inhibit TNF-α production via suppression of NF-κB activation through pathways distinct from cysLTR1 antagonism.

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