Mild cold‐stress depresses immune responses: Implications for cancer models involving laboratory mice

Abstract

Physiologically accurate mouse models of cancer are critical in the pre-clinical development of novel cancer therapies. However, current standardized animal-housing temperatures elicit chronic cold-associated stress in mice, which is further increased in the presence of tumor. This cold-stress significantly impacts experimental outcomes. Data from our lab and others suggests standard housing fundamentally alters murine physiology, and this can produce altered immune baselines in tumor and other disease models. Researchers may thus underestimate the efficacy of therapies that are benefitted by immune responses. A potential mediator, norepinephrine, also underlies stress pathways common in mice and humans. Therefore, research into mechanisms connecting cold-stress and norepinephrine signaling with immune-depression in mice could highlight new combination therapies for humans to simultaneously target stress while stimulating anti-tumor immunity.

BMAL1 links the circadian clock to viral airway pathology and asthma phenotypes

“…Additionally, we opted to group house our mice during CJL conditioning rather than individually house mice. We did this because of emerging literature that housing mice individually may impose an additional stress on the animals that could confound our interpretation of SeV infection after CJL 43, 49 . Nevertheless, it is possible that our CJL protocol is milder than previous procedures, and may therefore understate the effects of jet lag on viral bronchiolitis.…”

Influence of Average Income on Epidemics of Seasonal Influenza

“…The epidemic scale was correlated with the minimum temperature (CC ＝ -0.526) and temperature difference (CC ＝ 0.606) in January. Low temperature causes cold stress, which depresses immune responses (13,14). Furthermore, cold stress due to temperatures ＜09 C causes death from respiratory disease in humans (15,16).…”

Special Conference on Tumor Immunology and Immunotherapy: A New Chapter

“…She showed that mice housed at ST were less able to control Panc02 tumors compared to mice housed under TT conditions, as well as mice housed in ST that were given cisplatin. Increases in MDSCs and Tregs were found in ST mice compared to animals housed in TT (55, 56). A possible mechanism for the susceptibility of ST-housed mice is the production of norepinephrine as administration of propranolol, a β-blocker, led to the reversal of the ST-susceptibility to tumor challenge (52).…”