Dunn Adrian J, Swiergiel Artur H, Zhang Hao, Quan Ning
Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA 71130-3932, USA.
Neuroimmunomodulation. 2006;13(2):96-104. doi: 10.1159/000096291. Epub 2006 Oct 17.
Previous studies have shown that interleukin-1 (IL-1) and lipopolysaccharide (LPS) administration to animals induces behavioral changes, including a reduction in feeding. These effects of IL-1 and LPS have been shown to be sensitive to inhibitors of cyclooxygenase (COX).
To determine the relationships between induction of COX-2 in the brain with IL-1beta- and LPS-induced changes in body temperature, plasma corticosterone and feeding.
Mice were injected with intraperitoneal doses of IL-1beta and LPS that decreased feeding. The induction of COX-2 was studied immunocytochemically in the brain, in parallel with core body temperature, the drinking of sweetened milk, and plasma concentrations of corticosterone.
COX-2 immunoreactivity (ir) was sparse in the brains of the untreated mice, but IL-1beta and LPS both increased its expression. This COX-2 induction appeared to be confined to blood vessels, and was not markedly region specific. Induction was evident 30 min after IL-1 or LPS, and was greater at 90 than at 30 min. COX-2-ir in the parenchyma did not change significantly. Thus induction of COX-2 occurred in brain endothelia in parallel with the reduction in feeding. This is consistent with the previously determined sensitivity of IL-1-induced changes in feeding to selective COX-2 inhibitors, and the responses to IL-1 in COX-2-deficient mice. The time courses of the IL-1- and LPS-induced increases in plasma corticosterone paralleled those in the reduction in milk drinking, however, the changes in body temperature appeared later.
Endothelial COX-2 may be involved in IL-1- and LPS-induced decreases in milk drinking, and possibly in the HPA axis activation. The decreased milk drinking may occur when IL-1 and LPS bind to receptors on brain endothelial cells subsequently inducing COX-2 and the production of prostanoids which elicit the reductions in milk drinking. Thus the behavioral effects of peripherally administered IL-1 and LPS appear to be mediated by multiple mechanisms, including endothelial COX-2, and vagal afferents.
先前的研究表明，给动物注射白细胞介素-1（IL-1）和脂多糖（LPS）会引起行为变化，包括进食减少。IL-1和LPS的这些作用已被证明对环氧化酶（COX）抑制剂敏感。
确定脑内COX-2的诱导与IL-1β和LPS诱导的体温、血浆皮质酮和进食变化之间的关系。
给小鼠腹腔注射降低进食量的IL-1β和LPS剂量。采用免疫细胞化学方法研究脑内COX-2的诱导情况，并同时监测核心体温、甜牛奶饮用量和血浆皮质酮浓度。
在未处理小鼠的脑中，COX-2免疫反应性（ir）稀疏，但IL-1β和LPS均增加了其表达。这种COX-2的诱导似乎局限于血管，且无明显的区域特异性。IL-1或LPS注射后30分钟诱导明显，90分钟时比30分钟时更明显。实质内的COX-2-ir无明显变化。因此，COX-2的诱导在脑内皮细胞中与进食减少同时发生。这与先前确定的IL-1诱导的进食变化对选择性COX-2抑制剂的敏感性以及COX-2缺陷小鼠对IL-1的反应一致。IL-1和LPS诱导的血浆皮质酮升高的时间进程与牛奶饮用量减少的时间进程平行，然而，体温变化出现较晚。
内皮COX-2可能参与IL-1和LPS诱导的牛奶饮用量减少，可能还参与下丘脑-垂体-肾上腺（HPA）轴的激活。当IL-1和LPS与脑内皮细胞上的受体结合，随后诱导COX-2和前列腺素的产生，从而导致牛奶饮用量减少时，可能会出现牛奶饮用量减少的情况。因此，外周给予IL-1和LPS的行为效应似乎是由多种机制介导的，包括内皮COX-2和迷走神经传入。
