scholarly journals The Additional Effects of Clarithromycin And Pranlukast On The Cytokine Suppression By Corticosteroids Using Murine Allergic Bronchopulmonary Aspergillosis Model

2021 ◽  
Author(s):  
Chizu Fukushima ◽  
Yasushi Obase ◽  
Susumu Fukahori ◽  
Hiroyuki Yamaguchi ◽  
Noriho Sakamoto ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Combined Treatment ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Dermatophagoides Farinae ◽  
Leukotriene Receptor Antagonist ◽  
Inflammatory Protein ◽  
Oral Corticosteroids ◽  
Leukotriene Receptor ◽  
Anti Fungal ◽  
Macrophage Inflammatory Protein

Abstract Few medicines other than oral corticosteroids and anti-fungal medicines are currently known as reliable treatments for allergic bronchopulmonary aspergillosis (ABPA). The efficacies of macrolide or leukotriene receptor antagonist (LTRA) with or without corticosteroid on ABPA are unknown. Mice were sensitized to Dermatophagoides farinae (Df) allergen intranasally and infected with Aspergillus fumigatus (Af). After Af infection, corticosteroid (Dexamethasone; Dex) was administered for five days in DfAf/Dex group. The effects of macrolide (clarithromycin; CAM) or LTRA (pranlukast; PRN) with or without Dex were also evaluated. Pathologically, the combined treatment with Dex and CAM decreased the airway inflammation. The interleukin (IL)-5, IL-13 and macrophage inflammatory protein (MIP)-2 concentrations in homogenized lungs were significantly elevated in DfAf mice compared to control mice (p < 0.05, each). CAM significantly decreased the elevations of MIP-2 of DfAf mice (p < 0.05). The addition of CAM on Dex suppressed both of the MIP-2 and IL-5 elevation (p < 0.05, each, DfAf/Dex vs DfAf/Dex/CAM group), but the addition of PRN on Dex did not. It was suggested that combination of CAM and corticosteroid enhanced the suppressing effect of both eosinophilic and neutrophilic airway inflammations. This finding will give a new hope for the treatment of severe fungus-related asthma.

Montelukast, a Leukotriene-Receptor Antagonist, for the Treatment of Mild Asthma and Exercise-Induced Bronchoconstriction

1999 ◽  
Vol 43 (3) ◽  
pp. 185-186
Author(s):  
JONATHAN A. LEFF ◽  
WILLIAM W. BUSSE ◽  
DAVID PEARLMAN ◽  
EDWIN A. BRONSKY ◽  
JAMES KEMP ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Mild Asthma ◽  
Leukotriene Receptor Antagonist ◽  
Leukotriene Receptor ◽  
Exercise Induced

scholarly journals Effect of the leukotriene receptor antagonist ONO-1078 on extravascular lung water after coronary ligation in dogs.

1993 ◽  
Vol 57 (2) ◽  
pp. 161-166 ◽  
Author(s):  
HIROYA TANIGUCHI ◽  
YASUO TAKAYAMA ◽  
TOSHIJI IWASAKA ◽  
TERUHIRO TAMURA ◽  
HIROFUMI TAKASHIMA ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Extravascular Lung Water ◽  
Leukotriene Receptor Antagonist ◽  
Lung Water ◽  
Coronary Ligation ◽  
Leukotriene Receptor

scholarly journals The Leukotriene Receptor Antagonist Montelukast Attenuates Neuroinflammation and Affects Cognition in Transgenic 5xFAD Mice

2021 ◽  
Vol 22 (5) ◽  
pp. 2782 ◽  
Author(s):  
Johanna Michael ◽  
Julia Zirknitzer ◽  
Michael Stefan Unger ◽  
Rodolphe Poupardin ◽  
Tanja Rieß ◽  
...  
Keyword(s):  
T Cells ◽  
Receptor Antagonist ◽  
Cd8 T Cells ◽  
Disease Model ◽  
Cognitive Outcome ◽  
Drug Candidate ◽  
Potential Drug ◽  
Leukotriene Receptor Antagonist ◽  
Leukotriene Receptor ◽  
5Xfad Mice

Alzheimer’s disease (AD) is the most common form of dementia. In particular, neuroinflammation, mediated by microglia cells but also through CD8+ T-cells, actively contributes to disease pathology. Leukotrienes are involved in neuroinflammation and in the pathological hallmarks of AD. In consequence, leukotriene signaling—more specifically, the leukotriene receptors—has been recognized as a potential drug target to ameliorate AD pathology. Here, we analyzed the effects of the leukotriene receptor antagonist montelukast (MTK) on hippocampal gene expression in 5xFAD mice, a commonly used transgenic AD mouse model. We identified glial activation and neuroinflammation as the main pathways modulated by MTK. The treatment increased the number of Tmem119+ microglia and downregulated genes related to AD-associated microglia and to lipid droplet-accumulating microglia, suggesting that the MTK treatment targets and modulates microglia phenotypes in the disease model compared to the vehicle. MTK treatment further reduced infiltration of CD8+T-cells into the brain parenchyma. Finally, MTK treatment resulted in improved cognitive functions. In summary, we provide a proof of concept for MTK to be a potential drug candidate for AD and provide novel modes of action via modulation of microglia and CD8+ T-cells. Of note, 5xFAD females showed a more severe pathology, and in consequence, MTK treatment had a more pronounced effect in the females compared to the males. The effects on neuroinflammation, i.e., microglia and CD8+ T-cells, as well as the effects on cognitive outcome, were dose-dependent, therefore arguing for the use of higher doses of MTK in AD clinical trials compared to the approved asthma dose.

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