Cool Housing Temperature and Cold Stress Linked To Immunosuppression and Increased Tumor Growth in Experimental Animals

cold stress immunosuppression

In the December 2013 issue of the Proceedings of the National Academy of Sciences of the USA Kathleen Kokolus et al., from the Roswell Park Cancer Institute, Buffalo, NY and the US Environmental Protection Agency, NC, demonstrate that a cool ambient housing temperature may affect the outcome of a broad range of experimental endpoints, including antitumor immunity and experimental tumor growth in mice.

Experimental research with animal models can be affected by many factors but a variable that has received little attention is housing temperature in research facilities.

Research facilities use ‘standard’ housing temperatures for experimental animals around 20–26 °C. However, in nature, or natural ‘environments’, studies have shown that mice seek warm environments; and healthy mice usually select an ambient temperature of 30–31 °C.

The authors of this study have shown that mice housed at a standard temperature of ∼22–23 °C, when compared to mice kept at a thermoneutral temperature (∼30–31 °C), had not only less CD8+T cells (and more immune suppressive cells), but in the tumor microenvironment their T cells had suppressed interferon (IFN)-γ production. More importantly, these mice also had marked increase in tumor formation, growth rate and metastasis.

Thermoregulation is a complex phenomenon, and acute or chronic cold stress, including the activation of thermogenesis to maintain normal body temperature, involves mostly hyperactivity of the sympathetic nervous system (SNS), associated with release of catecholamines (Goldstein DS & Kopin IJ, 2008, Endocr Regul, 42:111; Kvetnansky, R et al., 2013, Adv Pharmacol, 68:359). Previous research indicates that the SNS affects various components of the innate, adaptive, and the cellular and humoral immunity (Elenkov IJ et al., 2000, Pharmacol Rev, 52:595-638), and that cold stress has a specific ‘neurochemical signature’ characterized by increased levels of neuropeptide Y (NPY), or NPY and norepinephrine/noradrenaline (Pacak, K et al., 1998, Am. J. Physiol. 275:R1247; Li, L et al., 2005, Arterioscler. Thromb. Vasc. Biol. 25:2075).

Kokolus et al., discuss that an increase in the activity of SNS/norepinephrine-driven cold stress response is most likely the underlying mechanism involved in their observations.

As mouse models may not correctly predict which new therapies will be effective in the clinic, this study, according to the authors, suggest that it is important to consider ambient temperature when cancer (and perhaps other disorders) are modeled in mice. Moreover, these results may also suggest that further studies on the interactions between (cold) stress, thermoregulation, and immune (antitumor) responses are warranted.

Source: Proc Natl Acad Sci U S A. 2013, 110:20176-81. doi: 10.1073/pnas.1304291110. Epub 2013 Nov 18.
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