“Thermoneutrality, Mice, and Cancer: A Heated Opinion”, 2016-04-22 (; similar):
Trends:
Several mouse models show statistically-significant differences in experimental outcomes at standard sub-thermoneutral (ST, 22–26℃) versus thermoneutral housing temperatures (TT, 30–32℃), including models of cardiovascular disease, obesity, inflammation and atherosclerosis, graft versus host disease and cancer.
NE levels are higher, anti-tumor immunity is impaired, and tumor growth is statistically-significantly enhanced in mice housed at ST compared to TT. NE levels are reduced, immunosuppression is reversed and tumor growth is slowed by housing mice at TT.
Housing temperature should be reported in every study such that potential sources of data bias or non-reproducibility can be identified.
Our opinion is that any experiment designed to understand tumor biology and/or having an immune component could potentially have different outcomes in mice housed at ST versus TT and this should be tested.
The ‘mild’ cold stress caused by standard sub-thermoneutral housing temperatures used for laboratory mice in research institutes is sufficient to statistically-significantly bias conclusions drawn from murine models of several human diseases. We review the data leading to this conclusion, discuss the implications for research and suggest ways to reduce problems in reproducibility and experimental transparency caused by this housing variable. We have found that these cool temperatures suppress endogenous immune responses, skewing tumor growth data and the severity of graft versus host disease, and also increase the therapeutic resistance of tumors. Owing to the potential for ambient temperature to affect energy homeostasis as well as adrenergic stress, both of which could contribute to biased outcomes in murine cancer models, housing temperature should be reported in all publications and considered as a potential source of variability in results between laboratories. Researchers and regulatory agencies should work together to determine whether changes in housing parameters would enhance the use of mouse models in cancer research, as well as for other diseases. Finally, for many years agencies such as the National Cancer Institute (NCI) have encouraged the development of newer and more sophisticated mouse models for cancer research, but we believe that, without an appreciation of how basic murine physiology is affected by ambient temperature, even data from these models is likely to be compromised.
[Keywords: thermoneutrality, tumor microenvironment, immunosuppression, energy balance, metabolism, adrenergic stress]