The effects of intense physical exercise on secondary antibody response in young and old mice.

BACKGROUND AND PURPOSE: Based largely on data from young subjects, intense physical exercise is believed to suppress immune function. In addition, immune function, including secondary antibody response, declines with advancing age. Therefore, intense exercise in old subjects may further suppress the secondary antibody response. The purpose of this in vivo study was to investigate the effects of intense physical exercise on secondary antibody response in young (6-8 weeks) and old (22-24 months) C57BL/6 mice. SUBJECTS AND METHODS: Data were obtained from 22 young and 18 old C57BL/6 mice that were immunized to human serum albumin (HSA) and randomly divided into 3 groups. Two groups were exposed to a single bout of intense exercise to exhaustion and immediately boosted with an injection of HSA. The first group did not exercise further, but the second group continued with daily bouts of intense exercise to exhaustion for 9 days. The third group (control group) did not undergo intense exercise, but received the booster injection of HSA at the same time as the other groups. Ten days after the HSA booster injection, when high level of antibodies are produced in secondary antibody response, serum anti-HSA antibodies were measured by enzyme-linked immunosorbent assay. RESULTS: Young mice did not show suppression of secondary antibody response following intense exercise. However, old mice, exposed to a single bout of intense exercise, had an enhanced response similar to the response seen in young control mice. CONCLUSION AND DISCUSSION: The widely accepted hypothesis of immunosuppression resulting from intense exercise may not be true for old mice.

Nasal diagrams: a tool for recording the distribution of nasal lesions in rats and mice.

Knowledge of patterns of lesion distribution can provide insight into the relative roles played by regional tissue dose and local tissue susceptibility in toxic responses to xenobiotics in the nose and assist assessment of potential human risk. A consistent approach is needed for recording lesion distribution patterns in the complex nasal airways of rats and mice. The present work provides a series of diagrams of the nasal passages of the Fischer-344 rat and B6C3F1 mouse, designed for mapping nasal lesions. The diagrams present each of the major cross-sectional airway profiles, provide adequate space for nasal mucosal lesion recording, and are suitable for duplication in a commercial photocopier. Sagittal diagrams are also provided to permit transfer of lesion location data observed in transverse sections onto the long axis of the nose. The distribution of lesions induced by a selected range of xenobiotics is presented. Approaches to application of the diagrams and interpretation of results obtained are discussed in relation to factors responsible for lesion distribution in the nose and their relevance to interspecies extrapolation. A modified approach to anatomical classification of the ethmoturbinates of the rodent is also presented.

Application of computational fluid dynamics to regional dosimetry of inhaled chemicals in the upper respiratory tract of the rat.

For certain inhaled air pollutants, such as reactive, water soluble gases, the distribution of nasal lesions observed in F344 rats may be closely related to regional gas uptake patterns in the nose. These uptake patterns can be influenced by the currents of air flowing through the upper respiratory tract during the breathing cycle. Since data on respiratory tract lesions in F344 rats are extrapolated to humans to make predictions of risk to human health, a better understanding of the factors affecting these responses is needed. To assess potential effects of nasal airflow on lesion location and severity, a methodology was developed for creation of computer simulations of steady-state airflow and gas transport using a three-dimensional finite element grid reconstructed from serial step-sections of the nasal passages of a male F344 rat. Simulations on a supercomputer used the computational fluid dynamics package FIDAP (FDI, Evanston, IL). Distinct streams of bulk flow evident in the simulations matched inspiratory streams reported for the F344 rat. Moreover, simulated regional flow velocities matched measured velocities in concurrent laboratory experiments with a hollow nasal mold. Computer-predicted flows were used in simulations of gas transport to nasal passage walls, with formaldehyde as a test case. Results from the uptake simulations were compared with the reported distribution of formaldehyde-induced nasal lesions observed in the F344 rat, and indicated that airflow-driven uptake patterns probably play an important role in determining the location of certain nasal lesions induced by formaldehyde. This work demonstrated the feasibility of applying computational fluid dynamics to airflow-driven dosimetry of inhaled chemicals in the upper respiratory tract.

Computer simulation of inspiratory airflow in all regions of the F344 rat nasal passages.

Data from laboratory animal experiments are often used in setting guidelines for safe levels of human exposure to inhaled materials. The F344 rat has been used extensively in laboratory experiments to determine effects of exposure to inhaled materials in the nasal passages. Many inhaled materials induce toxic responses in the olfactory (posterior) region of the rat nasal passages. The location of major airflow routes has been proposed as playing a dominant role in determining some olfactory lesion location patterns. Since nasal airflow patterns differ significantly among species, methods are needed to assess conditions under which these differences may significantly affect extrapolation of the effects of local dose in animals to potential disease outcome in humans. A computational fluid dynamics model of airflow and inhaled gas uptake has been used to predict dose to airway walls in the anterior F344 rat nasal passages (Kimbell et al., Toxicol. Appl. Pharmacol., 1993; 121, 253-263). To determine the role of nasal airflow patterns in affecting olfactory lesion distribution, this model was extended to include the olfactory region. Serial-step histological sections of the nasal passages of a F344 rat were used to construct the computer model. Simulations of inspiratory airflow throughout the rat nasal passages were consistent with previously reported experimental data. Four of the five major simulated flow streams present in the anterior nose (dorsal lateral, middle, ventral lateral, and ventral medial streams) flowed together to exit ventrally at the nasopharyngeal duct, bypassing the ethmoid recesses. The remaining dorsal medial stream split to flow both medially and laterally through the olfactory-epithelium-lined ethmoid recesses in a Z-shaped pattern when viewed sagitally. Simulated flow in the ethmoid recesses was more than an order of magnitude slower than flow in the anterior and ventral parts of the nasal passages. Somewhat higher volumes of flow were predicted in the dorsal medial stream when the nasal vestibule was reshaped to be upturned, and more flow was allocated to the dorsal medial stream with increased inspiratory airflow rate, suggesting that rats may be able to allocate more airflow to this stream by both modifying the shape of the nasal vestibule and increasing inhaled air velocity during sniffing. The present study provides the first description of flow in the complex olfactory region of the nose of the F344 rat. This model will be used to evaluate the role of airflow patterns in determining the distribution of xenobiotically induced olfactory mucosal lesions. This information, combined with models of disposition in the airway lining, will provide comprehensive dosimetry models for extrapolating animal response data to humans.