Thermoneutral Housing Temperature Improves Survival in a Murine Model of Polymicrobial Peritonitis

Abstract

Regulatory guidelines mandate housing for laboratory mice at temperatures below their thermoneutral zone, creating chronic cold stress. However, increases in housing temperature could alter immune responses. We hypothesized housing mice at temperatures within their thermoneutral zone would improve sepsis survival and alter immune responses. Male C57BL/6 mice were housed at 22°C or 30°C after cecal ligation and puncture (CLP) for 10 days. Survival of mice housed at 30°C (78%) after CLP was significantly increased compared with mice housed at 22°C (40%). Experimental groups were repeated with mice euthanized at 0, 12, 24, and 48 h post-surgery to examine select immune parameters. Raising housing temperature minimally altered systemic, peritoneal, or splenic cell counts. However, IL-6 levels in plasma and peritoneal lavage fluid were significantly lower at 12 h post-surgery in mice housed at 30°C compared with 22°C. Bacterial colony counts from peritoneal lavage fluid were significantly lower in mice housed at 30°C and in vivo studies suggested this was the result of increased phagocytosis by neutrophils. As previously demonstrated, adoptive transfer of fibrocytes significantly increased sepsis survival compared with saline at 22°C. However, there was no additive effect when adoptive transfer was performed at 30°C. Overall, the results demonstrated that thermoneutral housing improves survival after CLP by increasing local phagocytic activity and technical revisions may be necessary to standardize the severity of the model across different housing temperatures. These findings stress the pronounced impact housing temperature has on the CLP model and the importance of reporting housing temperature.

<strong></strong>Thiamine and High Dose Insulin Treatment for Sepsis<strong> </strong>

“…This interpretation is supported by the finding that mice, whose metabolic rate is 7 times that of humans, housed at 30 ° C had higher survival from sepsis compared to mice housed at 20 ° C. The mice housed in thermoneutral conditions had mean energy expenditures 1.8 times basal whereas in cooler temperatures their mean energy expenditures were 3.1 times basal [35].…”

<strong></strong>Thiamine and High Dose Insulin Treatment for Sepsis<strong> </strong>

“…This interpretation is supported by the finding that mice, whose metabolic rate is 7 times that of humans, housed at 30 ° C had higher survival from sepsis compared to mice housed at 20 ° C. The mice housed in thermoneutral conditions had mean energy expenditures 1.8 times basal whereas in cooler temperatures their mean energy expenditures were 3.1 times basal [35].…”

Mouse sepsis models: don't forget ambient temperature!

“…A similar result in terms of mortality rate was reported in response to LPS at the dosages used there (LPS 1-1.5 mg/kg): in mice kept at T a = 30 °C (~ 75%) compared with mice kept at T a = 22 °C (~ 50%). In contrast, Carpenter et al [13] reported that the survival rate of male C57BL/6 mice housed at 30 °C (78%) after abdominal sepsis was significantly increased compared with mice housed at 22 °C (40%). This is in line with findings after LPS administration [14].…”

Common Variables That Influence Sepsis Mortality in Mice

“……”

<strong></strong>Thiamine and High Dose Insulin Treatment for Sepsis<strong> </strong>

“…This interpretation is supported by the finding that mice, whose metabolic rate is 7 times that of humans, housed at 30 ° C had higher survival from sepsis compared to mice housed at 20 ° C. The mice housed in thermoneutral conditions had mean energy expenditures 1.8 times basal whereas in cooler temperatures their mean energy expenditures were 3.1 times basal [35].…”

Mouse sepsis models: don't forget ambient temperature!

“…A similar result in terms of mortality rate was reported in response to LPS at the dosages used there (LPS 1-1.5 mg/kg): in mice kept at T a = 30 °C (~ 75%) compared with mice kept at T a = 22 °C (~ 50%). In contrast, Carpenter et al [13] reported that the survival rate of male C57BL/6 mice housed at 30 °C (78%) after abdominal sepsis was significantly increased compared with mice housed at 22 °C (40%). This is in line with findings after LPS administration [14].…”

Common Variables That Influence Sepsis Mortality in Mice

“……”

<strong></strong>Thiamine and High Dose Insulin Treatment for Sepsis<strong> </strong>

“…This interpretation is supported by the finding that mice, whose metabolic rate is 7 times that of humans, housed at 30 ° C had higher survival from sepsis compared to mice housed at 20 ° C. The mice housed in thermoneutral conditions had mean energy expenditures 1.8 times basal whereas in cooler temperatures their mean energy expenditures were 3.1 times basal [35].…”

Mouse sepsis models: don't forget ambient temperature!

“…A similar result in terms of mortality rate was reported in response to LPS at the dosages used there (LPS 1-1.5 mg/kg): in mice kept at T a = 30 °C (~ 75%) compared with mice kept at T a = 22 °C (~ 50%). In contrast, Carpenter et al [13] reported that the survival rate of male C57BL/6 mice housed at 30 °C (78%) after abdominal sepsis was significantly increased compared with mice housed at 22 °C (40%). This is in line with findings after LPS administration [14].…”

Common Variables That Influence Sepsis Mortality in Mice

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