A warmer ambient temperature increases the passage of interleukin-1beta into the brains of old rats

Abstract

We have demonstrated that after intraperitoneal lipopolysaccharide (LPS) injection, old rats mount fevers similar to those of young rats at an ambient temperature (Ta) of 31 degrees C, but not at 21 degrees C. The same is true for intraperitoneal or intravenous IL-1beta administration. The underlying mechanism responsible for blunted fever in old rats may be a deficiency in communication between the periphery and the brain. Possibly, peripheral cytokine actions are altered in old rats, such that the signal that reaches the brain is diminished. Here, we hypothesized that at standard laboratory temperatures, not enough IL-1beta is reaching the brain for fever to occur and that a warmer Ta would increase the influx of IL-1beta into the brain, enabling old rats to generate fever. Young (3-5 mo) and old (23-29 mo) Long-Evans rats were maintained for 3 days at either Ta 21 or 31 degrees C prior to intravenous injection with radiolabeled IL-1beta to measure passage across the blood-brain barrier. Young rats showed similar influx of IL-1beta into the brain at the two Tas, but old rats showed significant influx only at the warmer Ta. These data suggest that the lack of fever at a cool Ta may be due to a reduced influx of IL-1beta into the brain.

Fig. 1.

Tb after ¹²⁵IL-1β in young and old rats at 21°C (A) and 31°C (B). Baseline temperatures are shown in the insets. 1-min Tb data were averaged over 5 min and expressed as change in temperature from time 0. The number of animals in each group decreases over time such that at time 0, n = 12 for young rats and n = 10 for old rats, and by 60 min, n = 1 for both young and old rats.

Fig. 2.

A: influx of IL-1β and BSA into whole brain of young and old rats at Ta 21°C. Each point on the line represents data from a single animal. IL-1β crossed the blood-brain barrier (BBB) in young rats but did not cross significantly in old rats. Entry of BSA was not significant at either age. Young rats had greater influx than did old rats (P < 0.01). B: influx rates of IL-1β for different regions of the brain in young and old rats at Ta 21°C. Old rats (n = 10) showed no significant influx into any region studied. Overall effect of age, P < 0.001. Young rats (n = 12) showed significant influx into whole brain, the hypothalamus, hippocampus, and cerebellum (*P < 0.05, **P < 0.01).

Fig. 3.

A: influx of IL-1β and BSA into whole brain of young and old rats at Ta 31°C. IL-1β crossed the BBB similarly in young and old rats. Entry of BSA was not significant at either age. B: influx rates of IL-1β for different regions of the brain in young and old rats at Ta 31°C. Both young and old rats showed significant influx to the hypothalamus and the hippocampus. Old rats also showed significant influx into the cerebellum and pons-medulla. There were no differences between age groups. **P < 0.01 significant influx for young rats. ##P < 0.01, #P < 0.05 significant influx for old rats.

Fig. 4.

Amount of ¹²⁵I that precipitated with TCA from plasma samples from young and old mice at Ta 21 (A) and 31°C (B) over time. The rate of degradation (calculated by the slope of the line) shows decreased amount of label precipitating with time. This was slower in the plasma of old rats at 21°C compared with old rats at 31°C and young rats at either Ta.