A significant role of leukemia inhibitory factor in the brain and periphery in endotoxin stimulation of adrenocorticotropin secretion in the rat.
Leukemia inhibitory factor (LIF) is considered as another important cytokine regulating the activity of the hypothalamo-pituitary-adrenal axis. In this study, we examined the effects of intravenous (iv) and intracerebroventricular (icv) administrations of anti-LIF antibody on plasma adrenocorticotropin (ACTH) responses induced by intraperitoneal administration of lipopolysaccharide (LPS, 250 microg/kg) in male rats. Fifteen minutes before the LPS injection, anti-rat LIF antibody or control serum was given iv or icv. The antibody was administered at two different concentrations, i.e. undiluted and five-times diluted. Irrespective of the route of administration, the anti-LIF antibody partially but significantly suppressed ACTH responses to LPS, and its suppressive effect was similar between its two different concentrations. These results indicate that the anti-LIF antibody already exerted its maximal effects at its diluted preparation, and hence that the role of LIF in LPS-stimulated ACTH secretion is essentially partial. This is the first study to demonstrate in vivo that LIF in both the brain and general circulation plays a significant role in mediating endotoxin-stimulated ACTH secretion in the rat.
Watanobe
H
H
Third Department of Internal Medicine, Hirosaki University School of Medicine, 5 Zaifu-cho, Hirosaki, Aomori, Japan. watanobe@infoaomori.ne.jp
Suda
T
T
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D000906:Antibodies / Q000494:pharmacology; D000918:Antibody Specificity; D001921:Brain / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D004731:Endotoxins / Q000494:pharmacology*; D006131:Growth Inhibitors / Q000276:immunology / Q000378:metabolism*; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000502:physiology; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008070:Lipopolysaccharides / Q000494:pharmacology; D008222:Lymphokines / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D000906:Antibodies; D004731:Endotoxins; D006131:Growth Inhibitors; D015850:Interleukin-6; D053605:Leukemia Inhibitory Factor; D008070:Lipopolysaccharides; D008222:Lymphokines; D000324:Adrenocorticotropic Hormone