Tsushima H, Mori M
Department of Pharmacology, Nagoya City University Medical School, Kawasumi, Mizuho-ku, 467-8601, Nagoya, Japan.
Pharmacol Biochem Behav. 2001 May-Jun;69(1-2):17-22. doi: 10.1016/s0091-3057(01)00500-7.
Injections of lipopolysaccharide (LPS, 3 microg) into the lateral ventricle elicited anorexia with fever and also decreased body weight in rats. The LPS-induced anorexia was inhibited by intracerebroventicular (i.c.v.) injections of anti-interleukin (IL)-1beta antibody (Ab), chelerythrine, genistein and tyrphostin 46, but not by injections of indomethacin. Consecutive injections of orthovanadate and LPS (0.3 microg, a dose of LPS that did not show any effect on food intake, body weight or body temperature) reduced body weight, but did not induce anorexia. On the other hand, injections of IL-1beta (50 ng) did not influence food intake, although they decreased body weight and produced fever. The IL-1beta-induced decrease in body weight was inhibited by injections of genistein, but not by injections of chelerythrine or indomethacin. These findings suggest that the LPS-induced anorexia is independent of hyperthermia and involves IL-1beta generation, tyrosine kinase (TK) and protein kinase C (PKC). This is the first in vivo evidence that activation of TK and PKC induced by LPS is linked to anorexia.
向大鼠侧脑室内注射脂多糖（LPS，3微克）会引发食欲不振并伴有发热，同时还会导致大鼠体重下降。LPS诱导的食欲不振可被脑室内（i.c.v.）注射抗白细胞介素（IL）-1β抗体（Ab）、白屈菜红碱、染料木黄酮和 tyrphostin 46所抑制，但吲哚美辛注射则无此作用。连续注射原钒酸盐和LPS（0.3微克，此剂量的LPS对食物摄入量、体重或体温无任何影响）可降低体重，但不会引起食欲不振。另一方面，注射IL-1β（50纳克）虽会降低体重并引发发热，但对食物摄入量无影响。染料木黄酮注射可抑制IL-1β诱导的体重下降，而白屈菜红碱或吲哚美辛注射则无此作用。这些发现表明，LPS诱导的食欲不振与体温过高无关，涉及IL-1β生成、酪氨酸激酶（TK）和蛋白激酶C（PKC）。这是LPS诱导的TK和PKC激活与食欲不振相关的首个体内证据。
