Restraint of Animals Required for Nose-Only Inhalation Toxicologic Studies Suppresses Pulmonary Antibacterial Defenses

Abstract

This study was designed to determine whether immobilization of animals in restraint holders, commonly used for nose-only inhalation toxicologic studies, alters the antibacterial defenses of the lungs. A second objective was to investigate if the stress-induced impairment of lung defenses could be reduced or eliminated either by allowing a suitable time to elapse (recovery) after restraint or by conditioning (training). Restraint of animals for 4 h before bacterial challenge suppressed the bactericidal activity of murine lungs for at least 12 h; by 20 h the antibacterial defenses were restored to normal. Training the animals in the restraint holders for 4 h/day for 2 days eliminated the bactericidal dysfunction. Restraining the animals after bacterial challenge also suppressed the bactericidal activity of the lungs, which took 4 days of training to abrogate. These data demonstrate that immobilization of animals impairs pulmonary antibacterial defenses and raises questions whether other pulmonary biologic responses assessed in nose-only exposure toxicologic studies may also be effected by restraint stress.