Biomaterial Database

Leukotriene D4 receptor antagonism reduces airway hyperresponsiveness in monkeys. 1994

C R Turner, and W B Smith, and C J Andresen, and A C Swindell, and J W Watson

Department of Immunology and Infectious Diseases, Pfizer Central Research, Groton, Connecticut 06340.

Airway hyperresponsiveness (AHR) and pulmonary inflammation are observations that are consistently associated with asthma and also occur in a well-characterized monkey model of asthma. The following study was performed to determine whether treatment with an LTD4 receptor antagonist, ICI 198,615, could attenuate antigen-induced pulmonary inflammation and AHR in monkeys using the following protocol. On day 0, the PC200 (the concentration of methacholine (MCh) that doubled respiratory system resistance, Rrs) was determined in 6 male, atopic, cynomolgus monkeys, previously characterized in historical control trials (Control #1) as airway hyperresponsive. Bronchoalveolar lavage (BAL) was then performed to determine total and differential leukocyte counts. On days 3, 5 and 7, each monkey received 10 mg/kg ICI 198,615 (im) 30 min prior to Ascaris suum (Ag) aerosol exposures which doubled Rrs. On day 10, the post-Ag PC200 to MCh was determined and BAL was repeated. Five weeks after this trial was complete, a bracketing control trial (Control #2) was performed in which the monkeys were administered vehicle prior to each Ag exposure. In comparison to the response in both control trials, treatment with the LTD4 antagonist significantly (P < 0.05) inhibited the development of AHR and also significantly reduced (P < 0.05) peripheral blood lymphocyte counts after Ag challenge. Treatment with ICI 198,615 reduced the Ag-induced increase in BAL eosinophils, but statistical significance was obtained only when treated animals were compared to Control #1, not Control #2.(ABSTRACT TRUNCATED AT 250 WORDS)

UI	MeSH Term	Description	Entries
D007191	Indazoles	A group of heterocyclic aromatic organic compounds consisting of the fusion of BENZENE and PYRAZOLES.	Indazole
D007958	Leukocyte Count	The number of WHITE BLOOD CELLS per unit volume in venous BLOOD. A differential leukocyte count measures the relative numbers of the different types of white cells.	Blood Cell Count, White,Differential Leukocyte Count,Leukocyte Count, Differential,Leukocyte Number,White Blood Cell Count,Count, Differential Leukocyte,Count, Leukocyte,Counts, Differential Leukocyte,Counts, Leukocyte,Differential Leukocyte Counts,Leukocyte Counts,Leukocyte Counts, Differential,Leukocyte Numbers,Number, Leukocyte,Numbers, Leukocyte
D007962	Leukocytes	White blood cells. These include granular leukocytes (BASOPHILS; EOSINOPHILS; and NEUTROPHILS) as well as non-granular leukocytes (LYMPHOCYTES and MONOCYTES).	Blood Cells, White,Blood Corpuscles, White,White Blood Cells,White Blood Corpuscles,Blood Cell, White,Blood Corpuscle, White,Corpuscle, White Blood,Corpuscles, White Blood,Leukocyte,White Blood Cell,White Blood Corpuscle
D008252	Macaca fascicularis	A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula.	Burmese Long-Tailed Macaque,Crab-Eating Monkey,Cynomolgus Monkey,M. f. aurea,M. fascicularis,Macaca fascicularis aurea,Monkey, Crab-Eating,Monkey, Cynomolgus,Crab-Eating Macaque,Burmese Long Tailed Macaque,Crab Eating Macaque,Crab Eating Monkey,Crab-Eating Macaques,Crab-Eating Monkeys,Cynomolgus Monkeys,Long-Tailed Macaque, Burmese,Macaque, Burmese Long-Tailed,Macaque, Crab-Eating,Monkey, Crab Eating
D008297	Male		Males
D008565	Membrane Proteins	Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.	Cell Membrane Protein,Cell Membrane Proteins,Cell Surface Protein,Cell Surface Proteins,Integral Membrane Proteins,Membrane-Associated Protein,Surface Protein,Surface Proteins,Integral Membrane Protein,Membrane Protein,Membrane-Associated Proteins,Membrane Associated Protein,Membrane Associated Proteins,Membrane Protein, Cell,Membrane Protein, Integral,Membrane Proteins, Integral,Protein, Cell Membrane,Protein, Cell Surface,Protein, Integral Membrane,Protein, Membrane,Protein, Membrane-Associated,Protein, Surface,Proteins, Cell Membrane,Proteins, Cell Surface,Proteins, Integral Membrane,Proteins, Membrane,Proteins, Membrane-Associated,Proteins, Surface,Surface Protein, Cell
D001992	Bronchoalveolar Lavage Fluid	Washing liquid obtained from irrigation of the lung, including the BRONCHI and the PULMONARY ALVEOLI. It is generally used to assess biochemical, inflammatory, or infection status of the lung.	Alveolar Lavage Fluid,Bronchial Lavage Fluid,Lung Lavage Fluid,Bronchial Alveolar Lavage Fluid,Lavage Fluid, Bronchial,Lavage Fluid, Lung,Pulmonary Lavage Fluid,Alveolar Lavage Fluids,Bronchial Lavage Fluids,Bronchoalveolar Lavage Fluids,Lavage Fluid, Alveolar,Lavage Fluid, Bronchoalveolar,Lavage Fluid, Pulmonary,Lavage Fluids, Alveolar,Lavage Fluids, Bronchial,Lavage Fluids, Bronchoalveolar,Lavage Fluids, Lung,Lavage Fluids, Pulmonary,Lung Lavage Fluids,Pulmonary Lavage Fluids
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D004804	Eosinophils	Granular leukocytes with a nucleus that usually has two lobes connected by a slender thread of chromatin, and cytoplasm containing coarse, round granules that are uniform in size and stainable by eosin.	Eosinophil
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia