Manipulation of Ambient Housing Temperature To Study the Impact of Chronic Stress on Immunity and Cancer in Mice

Abstract

Mice are the preeminent research organism in which to model human diseases and study the involvement of the immune response. Rapidly accumulating evidence indicates a significant involvement of stress hormones in cancer progression, resistance to therapies, and suppression of immune responses. As a result, there has been a concerted effort to model human stress in mice. In this article, we discuss recent literature showing how mice in research facilities are chronically stressed at baseline because of environmental factors. Focusing on housing temperature, we suggest that the stress of cool housing temperatures contributes to the impact of other imposed experimental stressors and therefore has a confounding effect on mouse stress models. Furthermore, we propose that manipulation of housing temperature is a useful approach for studying the impact of chronic stress on disease and the immune response and for testing therapeutic methods of reducing the negative effects of chronic stress.

Fig. 1:. Manipulation of ambient housing temperature regulates the degree of baseline stress experienced by laboratory mice.

Mice housed at mandated sub-thermoneutral temperatures (~22˚C) experience chronic stress and have elevated levels of the sympathetic neurotransmitter norepinephrine (NE). Thus majority of studies designed to study the effects of stress in mouse models impose stress on mice which already are under a moderate degree of stress, sufficient to promote tumor growth and suppress immune responses. In contrast, by housing mice at thermoneutrality, baseline adrenergic stress is alleviated. Reducing baseline stress in mice housed at 22˚C can be achieved by alternative methods. Approaches for imposing and reducing stress in laboratory mice are indicated followed by representative references (–, , , , –41, 63, 64, 68).