Pranlukast, a leukotriene receptor antagonist, inhibits interleukin-5 production via a mechanism distinct from leukotriene receptor antagonism.
BACKGROUND
Pranlukast, a cysteinyl leukotriene receptor 1 (CysLTR1) antagonist, inhibits not only airway smooth muscle contraction, but also allergic inflammation. The aim of this study was to determine the mechanism of pranlukast-induced interleukin-5 (IL-5) inhibition in allergic inflammation.


METHODS
Surgically resected human lung tissue was passively sensitized in vitro with mite-allergen-sensitized sera, followed by stimulation with mite allergen after pretreatment of the tissue with pranlukast, dexamethasone, or both. The IL-5 protein level in the culture medium was measured, and in situ hybridization of IL-5 and CysLTR1 mRNA was performed using lung tissues.


RESULTS
Pretreatment of lung tissues with pranlukast alone significantly decreased the amount of IL-5 protein in the culture medium by 40%. The combination of pranlukast and dexamethasone synergistically enhanced this effect. Quantitative in situ hybridization with image analysis revealed abundant expression of IL-5 mRNA in eosinophils, lymphocytes, and mast cells in sensitized and allergen-stimulated lung tissues. CysLTR1 mRNA was detected in macrophages, smooth muscle cells, eosinophils, and mast cells, but was less expressed in lymphocytes. Pranlukast-induced inhibition of IL-5 mRNA expression was noted in various cells, irrespective of their CysLTR1 mRNA expression status. In addition, cysteinyl leukotrienes per se failed to upregulate the IL-5 production.


CONCLUSIONS
Our results indicate that pranlukast inhibits IL-5 synthesis via a mechanism distinct from CysLTR1 antagonism.
Fukushima
Chizu
C
Second Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki, Japan.
Matsuse
Hiroto
H
Hishikawa
Yoshitaka
Y
Kondo
Yuki
Y
Machida
Ikuko
I
Saeki
Sachiko
S
Kawano
Tetsuya
T
Tomari
Shinya
S
Obase
Yasushi
Y
Shimoda
Terufumi
T
Koji
Takehiko
T
Kohno
Shigeru
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002867:Chromones / Q000276:immunology / Q000494:pharmacology*; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D015848:Interleukin-5 / Q000096:biosynthesis* / Q000276:immunology; D020024:Leukotriene Antagonists / Q000276:immunology / Q000494:pharmacology*; D008168:Lung / Q000187:drug effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D018077:Receptors, Leukotriene / Q000276:immunology
D002867:Chromones; D015848:Interleukin-5; D020024:Leukotriene Antagonists; D018077:Receptors, Leukotriene; C047681:pranlukast