Cysteinyl leukotriene receptor antagonist regulates allergic airway inflammation in an organ- and cytokine-specific manner
Tetsuya Kawano, Hiroto Matsuse, Tomoko Tsuchida, Susumu Fukahori, Chizu Fukushima, Tomoya Nishino, Shigeru Kohno
Second Department of Internal Medicine, Nagasaki University Hospital, Nagasaki, Japan
Med Sci Monit 2014; 20:297-302
Available online: 2014-02-22
Cysteinyl leukotrienes (cys-LTs) are very important factors in the pathophysiology of bronchial asthma. Cys-LT receptor antagonists (LTRAs) decrease allergic airway inflammation. The aim of the present study was to determine the differential effects of LTRAs and corticosteroids on allergic airway inflammation and allergen-specific cytokine production from lymphoid tissues using a murine model of asthma.
Material and Methods: Four groups of female BALB/c mice [control (Cont); Dermatophagoides farinae allergen-sensitized (AS); pranlukast (Prl), an LTRA-treated AS; and dexamethasone (Dex)-treated AS] were examined. Lung pathology and cytokine production by prepared mononuclear cells isolated from mediastinal lymph nodes (MLNs) and spleen were compared among these groups.
Results: AS mice exhibited allergic airway inflammation and significant increases in allergen-specific Th1 and Th2 cytokines in MLNs and spleen. Prl-treated mice showed significant attenuation of allergic airway inflammation concomitant with reduction of Th2 cytokines and IFN-g in MLNs but not in spleen. In contrast, Dex significantly decreased Th1 and Th2 cytokines in MLNs and also decreased them (except IL-13 and IL-2) in spleen.
Conclusions: The inflammatory effects of cys-LTs could differ in lymphoid organs. LTRAs potentially regulate allergic airway inflammation in an organ- and cytokine-specific manner, while systemic corticosteroid shows nonspecific effects.
Keywords: Adrenal Cortex Hormones - pharmacology, Asthma, Analysis of Variance, Animals, Asthma - physiopathology, Bronchoalveolar Lavage Fluid - cytology, Cell Count, Chromones - pharmacology, Cytokines - metabolism, Leukocytes, Mononuclear - metabolism, Leukotriene Antagonists - pharmacology, Lung - pathology, Lymph Nodes - cytology, Mice, Mice, Inbred BALB C, Receptors, Leukotriene - metabolism, Spleen - cytology