Inhibition of tumor necrosis factor-alpha and interleukin-1-beta production by beta-adrenoceptor agonists from lipopolysaccharide-stimulated human peripheral blood mononuclear cells

被引：65

作者：

Yoshimura, T ^{[1
]}

Kurita, C ^{[1
]}

Nagao, T ^{[1
]}

Usami, E ^{[1
]}

Nakao, T ^{[1
]}

Watanabe, S ^{[1
]}

Kobayashi, J ^{[1
]}

Yamazaki, F ^{[1
]}

Tanaka, H ^{[1
]}

Inagaki, N ^{[1
]}

Nagai, H ^{[1
]}

机构：

[1] GIFU PHARMACEUT UNIV, DEPT PHARMACOL, GIFU 502, JAPAN

来源：

PHARMACOLOGY | 1997年 / 54卷 / 03期

关键词：

beta-adrenoceptor agonist; tumor necrosis factor-alpha; interleukin-1; beta; interleukin-8; cyclic AMP; peripheral blood mononuclear cells; human;

D O I：

10.1159/000139481

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

The effects of beta-adrenoceptor agonists (beta-agonists) on the production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-8 (IL-8) by lipopolysaccharide (LPS)-stimulated human peripheral blood mononuclear cells (PBMCs) were investigated. The beta-agonists, procaterol, clenbuterol, fenoterol and terbutaline, inhibited TNF-alpha and IL-1 beta production in a concentration-dependent manner, whereas they had no effect on IL-8 production. TNF-alpha production was inhibited more potently than IL-1 beta. Dibutyryl cyclic AMP (dbcAMP) also inhibited the production of TNF-alpha and IL-1 beta, but not IL-8. TNF-alpha production was almost completely inhibited by dbcAMP, whereas IL-1 beta production appeared to be partially refractory even at the highest concentration examined. Both procaterol and theophylline elevated cAMP levels in LPS-stimulated PBMCs, but the effect of procaterol was limited. The inhibition of TNF-alpha and IL-1 beta production by procaterol was additively potentiated with theophylline. dl-Propranolol, a beta-adrenoceptor antagonist, abrogated the inhibition of TNF-alpha and IL-1 beta production by procaterol. These results indicate that beta-agonists inhibit the production of proinflammatory cytokines, such as TNF-alpha and IL-1 beta, by elevating intracellular cAMP levels. These properties of beta-agonists might be beneficial in the treatment of allergic inflammation.

引用

页码：144 / 152

页数：9

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