Comparison between the hypothermic and normothermic stress paradigms. (A) Mice were subjected to hypothermic (HWC) or normothermic (NWC) wet-cage stress, and core temperatures were measured at 0, 4, and 8 h following stress initiation. (B–D) Mice were subjected to 8 h of HWC, NWC, or served as HCC, and were administered with CpG-C or vehicle 2 h after the onset of stress. Visible hepatic metastases were counted 20 days later for males and 25 days later for females. (A) HWC significantly reduced core body temperatures at 4 h (n=15, n=7–8 per group, P=0.003) and at 8 h (P<0.0001) compared to NWC. (B) Both HWC and NWC significantly elevated plasma corticosterone levels to a similar degree (main effect – n=43, n=7–8 per group, P<0.0001, Tukey – P=0.6024, P=0.9935). (C) CpG-C significantly increased plasma IL-12 levels (main effect – n=43, n=7–8 per group, P<0.0001), and in animals administered with CpG-C, NWC decreased plasma IL-12 levels compared to HCC (P<0.0001), and HWC decreased it significantly more (P=0.0087). Similarly, CpG-C significantly reduced the number of hepatic metastases (D) (main effect – n=67, n=11–12 per group, P<0.0001), and in animals administered with CpG-C NWC increased the number of hepatic metastases compared to HCC (P=0.0126), and HWC elevated this number significantly more (P=0.0036) (*P<0.05; **P<0.001, ***P<0.001; ****P<0.0001). (A) Graphs represent mean±SEM. (B–D) Boxes represent the second and third quartiles, and whiskers show min and max values.