Effects of immobilization restraint on Syrian golden hamsters.

Rodent nose-only inhalation toxicology systems comprise whole-body immobilization in plastic restraint tubes. This method of restraint is known to have a variety of effects on animals. In the studies reported here, two independent toxicology laboratories examined the effects of inhalation tube restraint in Syrian golden hamsters, a species that has recently gained importance in inhalation studies of fibrous particulates. Body weight, food and water consumption, core body temperature, and plasma cortisol and corticosterone concentrations were assessed in animals immobilized in nose-only inhalation tubes, and the results were compared with those from unrestrained cage-control animals. Animals were immobilized for either 6 h/ day, 5 days/week for 13 weeks (subchronic), or 4 h/day for 14 consecutive days (subacute), mimicking exposure conditions commonly used in nose-only inhalation studies. Tube restraint was found to induce a marked decrease in body weight, which increased in response to cessation of restraint. The body weight decrement was associated with significant differences in food and water consumption between the restrained and control groups in the subacute study and only food consumption in the subchronic study. During the restraint period, core body temperature in the immobilized animals increased slightly but not above the normal range for this species. Plasma cortisol and corticosterone concentrations were not significantly increased with use of restraint, compared with values in controls. Immobilization-associated body weight depression in Syrian golden hamsters is important for the evaluation of nose-only inhalation study results because many normal physiologic parameters, as well as toxicant-induced effects, are associated with body weight status.

Inflammation and recruitment of immune cells into the lung.

The mechanisms responsible for recruitment of antibody-forming cells (AFC) into lung lobes exposed to antigen are not known. Because instillation of antigen induces inflammation, AFC may enter immunized lung lobes by changes in vascular permeability and/or in response to the release of mediators. The purposes of this study were to evaluate inflammatory responses produced by particulate antigens or interleukin-1 (IL-1) and to examine the recruitment of AFC and lymphocytes into the lung in response to these inflammatory stimuli. Two peaks of inflammation were observed in the lung lobes of dogs exposed to sheep red blood cells (SRBC), one at 1 day and the second around 9 days after instillation. Lymphocytes did not enter the lung during the first inflammatory response. However, lymphocytes and anti-SRBC AFC did enter immunized lung lobes during the second inflammatory response. AFC and lymphocytes also entered a lung lobe instilled with rabbit red blood cells (RRBC) at 6 days after immunization with SRBC. The observation that lymphocytes did not enter at 1 day after instillation of SRBC, but did enter the RRBC lung lobe at 1 day after instillation of RRBC, suggested that a population of lymphocytes, including AFC, were present in blood several days after immunization with SRBC that were capable of entering sites of inflammation in the lung. Instilled IL-1 was chemotactic in vivo for neutrophils and induced inflammation in the lung. However, IL-1 was not directly chemotactic for AFC or lymphocytes in vivo.