Effects of acute psychosocial stress in a nonhuman primate model of allergic asthma.

Current husbandry and care guidelines for laboratory animals recommend social housing for nonhuman primates and all other social species. However, not all individuals of a social species are compatible, which can lead to psychosocial stress on certain members. Because stress affects immune responses, we undertook the present study to determine whether psychosocial stress associated with changes in the group housing of nonhuman primates affected allergic responses in a nonhuman primate model of allergic asthma. Historic records from 35 cynomolgus macaques (Macaca fascicularis) sensitive to house dust mites (HDM) and enrolled in asthma studies from 2007 to 2011 were reviewed for variations in response to aerosolized HDM that could not be explained by clinical or experimental interventions. We then compared these variations with husbandry and clinical records to determine whether the unexplained variations in responses were associated with events known to induce psychosocial stress in this species, including restructuring of social groups, temporary isolation of group members, and changes in cage or room configurations. Adult macaques in stable social groups exhibited little variation in responses to aerosolized antigen. Changes in group membership (conspecifics), cage configurations, and temporary isolation of a group member were associated with decreased responses to HDM. This attenuation lasted 2 to 3 mo on average, although some macaques showed prolonged responses. No evidence for a stress-induced increase in allergic responses was noted. These results demonstrate that acute stress in HDM-sensitive cynomolgus macaques diminishes the physiologic response to inhaled allergen.

Nocturnal thoracoabdominal asynchrony in house dust mite-sensitive nonhuman primates.

Nocturnal bronchoconstriction is a common symptom of asthma in humans, but is poorly documented in animal models. Thoracoabdominal asynchrony (TAA) is a noninvasive clinical indication of airway obstruction. In this study, respiratory inductive plethysmography (RIP) was used to document nocturnal TAA in house dust mite (HDM)-sensitive Cynomolgus macaques. Dynamic compliance (C(dyn)) and lung resistance (R(L)) measured in anesthetized animals at rest and following exposure to HDM allergen, methacholine, and albuterol were highly correlated with three RIP parameters associated with TAA, ie, phase angle of the rib cage and abdomen waveforms (PhAng), baseline effort phase relation (eBPRL) and effort phase relation (ePhRL). Twenty-one allergic subjects were challenged with HDM early in the morning, and eBPRL and ePhRL were monitored for 20 hours after provocation. Fifteen of the allergic subjects exhibited gradual increases in eBPRL and ePhRL between midnight and 6 am, with peak activity at 4 am. However, as in humans, this nocturnal response was highly variable both between subjects and within subjects over time. The results document that TAA in this nonhuman primate model of asthma is highly correlated with C(dyn) and R(L), and demonstrate that animals exhibiting acute responses to allergen exposure during the day also exhibit nocturnal TAA.