Eosinophilic Airway Inflammation in a Cynomolgus Monkey

Abstract

The present article describes an occurrence of eosinophilic airway inflammation of a 4-year-old female cynomolgus monkey in a vehicle control group of a routine toxicology study. Histologically, the airway lesion was characterized by prominent eosinophilic infiltrates, accompanied by mast cells, lymphocytes, and plasmacytes. The eosinophilic infiltrates were distributed throughout the airway: from trachea through respiratory bronchioles in the lung. The morphological feature of the lesion was indicative of an allergic airway disorder that can occur in humans with asthma. The present case is remarkable in that there is a paucity of reports on naturally occurring allergic airway disorders in nonhuman primates. Keywords airway, cynomolgus, eosinophilic, inflammationHuman allergic disorders, such as anaphylaxis, hay fever, eczema, and asthma, have been increasing in the developed world, with roughly 25% of the population currently being affected. 4 For many asthma patients, the disease has its roots in infancy, and factors both genetic and environmental contribute to its inception and evolution.2 Allergic asthma can be referred to as abnormal adaptive immune responses in the airway. Briefly, this begins with presentation of an allergen to naive CD4þ helper T cells by dendritic cells. Then, T-helper-2 (T H 2) cells are generated and cytokines (IL-4, IL-5, IL-13) are released from T H 2 cells. These cytokines induce activation of eosinophils (IL-5) and immunoglobulin E-producing (IgE-producing) B cells (IL-4 and IL-13) and mast cells (IL-4); subsequently, IgE binds to mast cells. After that, exposure of IgE-coated mast cells to the allergen leads to the release of proinflammatory mediators (including those stored in the cytoplasmic granules), lipid-derived mediators, and newly synthesized cytokines, chemokines, and growth factors, as well as other mediators. These induce the recruitment and activation of T H 2 cells, eosinophils, and other leucocytes and the persistent mediator production by resident cells (such as mast cells). Prolonged or repetitive exposure to specific allergens ultimately results in airway remodeling, characterized by goblet cell hyperplasia and increases in submucosal tissue, the adventitia, and smooth muscle. 4,13The animal was a captive-bred 4-year-old female cynomolgus monkey (Macaca fascicularis), which was originally from Mauritius, obtained via commercial supplier and kept at our facilities for 18 months, then assigned to a vehicle (0.5% methylcellulose) control group consisting of 3 females for a 1-month oral toxicity study. The monkeys were housed in same-sex pairs in stainless-steel cages in a single room with a temperature of 70 + 5 F (21 + 3 C), a relative humidity of 50 + 10%, a minimum of 12 air changes per hour with air filtered through 90 to 95% efficiency filters, then through highefficiency particulate air (HEPA) filters, and an approximately 12-hour light/dark cycle. A standard diet of pelleted food (Certified Primate Diet 5K91, PMI Feeds, Inc, Gray Summit, MO) supplemen...

International Harmonization of Nomenclature and Diagnostic Criteria (INHAND): Non-proliferative and Proliferative Lesions of the Non-human Primate (<i>M. fascicularis</i>)

“…Comments: Smooth muscle cell hypertrophy/hyperplasia is uncommon as a spontaneous finding but can be seen in cases of lung inflammation, allergic disease and/or immune stimulation 455 , 456 , especially following inhalation administration of certain xenobiotics. Often it is observed as a focal/multifocal change rather than diffusely present throughout all areas of the parenchyma.…”