Age-Related Reciprocal Modulation of lnterleukin-1βand lnterleukin-1 Receptors in the Mouse Brain-Endocrine-Immune Axis

Abstract

The cytokine interleukin-1 (IL-1) alters a variety of immune, central nervous system and neuroendocrine activities characteristic of an integrator of the brain-endocrine-immune response to stress. In an attempt to define the regulation of IL-1 and IL-1 receptors in the mouse brain-endocrine-immune axis during maturation, we measured tissue levels of IL-lβusing an ELISA and iodine- 125-labeled recombinant human interleukin-1α([¹²⁵I]IL-lα) binding in hippocampus, pituitary, testis and spleen following intraperitoneal injection of saline or the bacterial endotoxin, lipopolysaccharide (LPS) in 3- and 24-week-old C57BL/6 mice. Basal IL-lβlevels were detectable in all the tissues examined. Basal levels of IL-1β in the hippocampus, spleen and testis in 24-week-old mice were significantly higher than those in 3-week-old mice. [¹²⁵I]IL-lαbinding was detectable in all the mouse tissues examined and [¹²⁵I]IL-1αbinding levels in the pituitary, spleen and testis in 3-week-old mice were significantly higher than those in 24-week-old mice. To further evaluate the modulation of IL-1 receptors in aging, we measured [¹²⁵I]IL-1αbinding in 2-, 5-, 10-, 18-, and 24-month-old mice. [¹²⁵I]IL-1αbinding in testis in 24-month-old mice was higher than the other groups; [¹²⁵I]IL-1αbinding in the hippocampus and spleen was unchanged during these periods. Dramatic increases in IL-lβconcentrations were observed at 2 h after LPS injection in the pituitary, spleen, testis and plasma in both 3- and 24-week-old mice groups. In contrast, IL-lβlevels in the hippocampus increased in response to LPS injection only in 24-week-old mice. [¹²⁵I]IL-1αbinding in hippocampus was significantly decreased in 24- but not in 3-week-old mice after LPS injection. [¹²⁵I]IL-1αbinding in the spleen and testis were significantly decreased in both age groups following LPS administration. These data demonstrate differential regulation of IL-1 and its receptors in the brain-endocrine-immune axis during maturation and in response to endotoxin challenge.