Effect of Orchidectomy on the Age-Related Modulation of IL-1β and IL-1 Receptors following Lipopolysaccharide Treatment in the Mouse

Abstract

Objective: To compare the effect of orchidectomy (ODX) in 7- and 24-week-old C57BL/6 mice on the age-related responses of the cytokine interleukin (IL)-1β and its receptor to intraperitoneal injection of the bacterial endotoxin, lipopolysaccharide (LPS). Methods: We measured IL-1β concentrations in the plasma, hippocampus, hypothalamus and adrenal gland using ELISA and iodine-125-labeled recombinant human IL-1α ([¹²⁵I]IL-1α) binding in the hippocampus following the intraperitoneal administration of saline or LPS. Results: There were no significant differences in the concentrations of IL-1β and its receptors in the brain and peripheral tissues between sham-operated and ODX mice in both age groups injected with saline. LPS induced significantly higher IL-1β production in the plasma and hippocampus in sham-operated 24-week-old mice than in 7-week-old mice. Coincident with the heightened IL-1β response to LPS, hippocampal [¹²⁵I]IL-1α binding was lower in 24-week-old mice than in 7-week-old mice after LPS injection in the sham-operated group. The age-related differences in the IL-1β concentrations in the plasma and hippocampus and [¹²⁵I]IL-1α binding in the hippocampus in response to LPS administration were abolished by ODX. Although LPS dramatically increased IL-1β levels in the hypothalamus, no significant age-related differences in IL-1β concentrations were seen, and ODX did not affect IL-1β levels. In contrast, there were no significant differences between saline- and LPS-injected 7-week-old mice in relation to concentrations in the adrenal gland. Moreover, although the adrenal IL-1β concentrations in 24-week-old mice were significantly higher than those in 7-week-old mice, ODX did not abolish these age-related differences in concentrations in the adrenal gland. Conclusions: Our data suggest the involvement of testosterone (or gonadal product) in plasma and hippocampal IL-1β regulation in relation to age, and demonstrate the importance of the gonadal development in mediating the effects of infectious challenge on the brain and immune function.

Gonadal hormone-dependent and -independent regulation of immune function by photoperiod in Siberian hamsters

“…Testosterone also exacerbates the symptoms of simulated bacterial infection. In vivo, LPS treatments induce greater febrile responses in male relative to female mice (31,32) and humans (1,17), and testosterone enhances LPS-elicited TNF-␣ responses in ungulates (27). Effects of sex steroids on inflammatory responses may occur directly on substrates within the immune system, and/or indirectly, e.g., potentiation of anti-inflammatory HPA responses to inflammatory signals such as LPS or IL-1␤ (48,49).…”

eae36, a Locus on Mouse Chromosome 4, Controls Susceptibility to Experimental Allergic Encephalomyelitis in Older Mice and Mice Immunized in the Winter

“…Peripheral immunological functions decline with age (Miller 1996), whereas within the brain immunologically important cells such as astrocytes (Goss et al 1991;O'Callaghan and Miller 1991;Nichols et al 1993;Morgan et al 1997) and microglia (Mattiace et al 1990;Peters et al 1991;Ogura et al 1994;Rozovsky et al 1998;Sheffield and Berman 1998;Sheng et al 1998) exhibit increased activation with age. Age-related changes associated with microglial activation include increased phagocytic activity ), expression of MHC class II genes (Mattiace et al 1990;Sheffield and Berman 1998), and secretion of proinflammatory cytokines (Takao et al 1996;Sheng et al 1998;Nanamiya et al 2000). Additionally, increased expression of cytokine and chemokine genes and their receptors occurs within the aging cortex, midbrain, hippocampus, and cerebellum (Felzien et al 2001;Terao et al 2002).…”