Inhibition of tumor necrosis factor-alpha and interleukin-1-beta production by beta-adrenoceptor agonists from lipopolysaccharide-stimulated human peripheral blood mononuclear cells.
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.
Yoshimura
T
T
Pharmaceutical Division, Ogaki Municipal Hospital, Gifu, Japan.
Kurita
C
C
Nagao
T
T
Usami
E
E
Nakao
T
T
Watanabe
S
S
Kobayashi
J
J
Yamazaki
F
F
Tanaka
H
H
Inagaki
N
N
Nagai
H
H
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D002469:Cell Separation; D002478:Cells, Cultured; D002976:Clenbuterol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004347:Drug Interactions; D004797:Enzyme-Linked Immunosorbent Assay; D005280:Fenoterol / Q000494:pharmacology; D006801:Humans; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D016209:Interleukin-8 / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000633:toxicity; D017265:Procaterol / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D013726:Terbutaline / Q000494:pharmacology; D013806:Theophylline / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D007375:Interleukin-1; D016209:Interleukin-8; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D014665:Vasodilator Agents; D005280:Fenoterol; D011433:Propranolol; D013806:Theophylline; D000242:Cyclic AMP; D013726:Terbutaline; D017265:Procaterol; D002976:Clenbuterol