Corticosteroid-independent inhibition of tumor necrosis factor production by the neuropeptide urocortin

被引:55
作者
Agnello, D
Bertini, R
Sacco, S
Meazza, C
Villa, P
Ghezzi, P
机构
[1] Mario Negri Inst Pharmacol Res, I-20157 Milan, Italy
[2] Dompe SPA Res Ctr, Dept Pharmacol, I-67100 Laquila, Italy
[3] CNR, Cellular & Mol Pharmacol Ctr, I-20129 Milan, Italy
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 1998年 / 275卷 / 05期
关键词
inflammation; cytokines; corticotropin-releasing factor; lipopolysaccharide; hypothalamus-pituitary-adrenal axis; interleukin-1; interleukin-6; Kupffer cells;
D O I
10.1152/ajpendo.1998.275.5.E757
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Urocortin (UCN) is a neuropeptide homologous with corticotropin-releasing factor (CRF), which has anti-inflammatory activities not all mediated by corticosteroids. In mice, UCN (1 mu g/mouse sc) significantly reduced lipopolysaccharide (LPS)-induced serum tumor necrosis factor (TNF) and interleukin (IL)-1 beta levels in vivo but did not affect serum IL-6. These effects were paralleled by a rise in corticosterone (CS) levels. Blockade of the CS increase by cyanoketone did not prevent TNF inhibition by UCN, suggesting the neuropeptide has anti-inflammatory mechanisms independent of the hypothalamus-pituitary-adrenal axis. In fact UCN had a direct inhibitory effect on LPS-induced TNF in rat Kupffer cells at concentrations between 10(-10) and 10(-16) M, and this effect was related to increased cAMP levels. However, the in vivo inhibition of LPS-induced IL-1 beta by UCN was reversed by cyanoketone, indicating that the increase of endogenous glucocorticoids might be more important in IL-1 beta inhibition than in TNF inhibition by UCN.
引用
收藏
页码:E757 / E762
页数:6
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