Effect of orchidectomy on the age-related modulation of IL-1beta and IL-1 receptors following lipopolysaccharide treatment in the mouse.
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)-1beta and its receptor to intraperitoneal injection of the bacterial endotoxin, lipopolysaccharide (LPS).


METHODS
We measured IL-1beta concentrations in the plasma, hippocampus, hypothalamus and adrenal gland using ELISA and iodine-125-labeled recombinant human IL-1alpha ([(125)I]IL-1alpha) binding in the hippocampus following the intraperitoneal administration of saline or LPS.


RESULTS
There were no significant differences in the concentrations of IL-1beta 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-1beta production in the plasma and hippocampus in sham-operated 24-week-old mice than in 7-week-old mice. Coincident with the heightened IL-1beta response to LPS, hippocampal [(125)I]IL-1alpha 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-1beta concentrations in the plasma and hippocampus and [(125)I]IL-1alpha binding in the hippocampus in response to LPS administration were abolished by ODX. Although LPS dramatically increased IL-1beta levels in the hypothalamus, no significant age-related differences in IL-1beta concentrations were seen, and ODX did not affect IL-1beta 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-1beta 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-1beta 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.
Nanamiya
W
W
Second Department of Internal Medicine, Kochi Medical School, Nankoku, Japan. nanamiya@med.kochi-ms.ac.jp
Takao
T
T
Asaba
K
K
De Souza
E B
EB
Hashimoto
K
K
D000311:Adrenal Glands / Q000276:immunology / Q000378:metabolism*; D000375:Aging / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D006624:Hippocampus / Q000276:immunology / Q000378:metabolism; D007031:Hypothalamus / Q000276:immunology / Q000378:metabolism*; D007375:Interleukin-1 / Q000097:blood*; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009919:Orchiectomy; D011869:Radioligand Assay; D017472:Receptors, Interleukin-1 / Q000097:blood*; D013739:Testosterone / Q000097:blood
D007375:Interleukin-1; D007457:Iodine Radioisotopes; D008070:Lipopolysaccharides; D017472:Receptors, Interleukin-1; D013739:Testosterone