Nephrol Dial Transplant (2000) 15: 1928-1934
© 2000 European Renal Association-European Dialysis and Transplant Association
ß2-Adrenoceptor agonist suppresses renal tumour necrosis factor and enhances interleukin-6 gene expression induced by endotoxin
1 Department of Paediatrics, Teikyo University School of Medicine, Tokyo, 3 Department of Immunology, National Children's Medical Centre, Tokyo, Japan and 2 Department of Physiology, University of Birmingham, Birmingham, UK
Background. ß2-Adrenoceptor activation regulates tumour necrosis factor (TNF)-
and interleukin-6 (IL-6) production in cultured renal cells. However, it remains uncertain whether, in vivo, the administration of ß2-adrenoceptor agonists regulate renal TNF- and IL-6 mRNA following lipopolysaccharide (LPS) stimulation to cause endotoxaemia. This study was performed in order to evaluate the effect of ß2-adrenoceptor agonist on renal TNF- and IL-6 production.
Methods. Four-week-old Wistar rats pre-treated with the ß2-adrenoceptor agonist terbutaline or formoterol, and/or the ß- and ß2-adrenoceptor antagonists (propanolol, ICI118,551), were injected with LPS (1 mg i.p.), and then 2, 4 or 6 h later, kidneys (cortex, medulla), spleen, thymus and plasma were collected to assay TNF- and IL-6 mRNA levels and their respective protein release.
Results. Administration of ß2-adrenoceptor agonists suppressed TNF- mRNA expression in the whole kidney, by 61% (P<0.05), as well as plasma, spleen and thymus TNF- protein and mRNA expression 2 hours after injection of LPS. On the other hand, although IL-6 levels in plasma, spleen and thymus mRNA expression were suppressed significantly by administration of ß2-adrenoceptor agonists, the basal- and LPS-induced IL-6 mRNA levels in the whole kidney were increased 1.6- and 1.2-fold (P<0.05), respectively, by treatment with ß2-adrenoceptor agonists. ß2-Adrenoceptor agonist suppressed LPS-induced TNF- mRNA expression by 35% (P<0.05) and stimulated LPS-induced IL-6 mRNA expression by 1.5-fold (P<0.05) in the medullary region of kidney.
Conclusions. ß2-Adrenoceptor agonists down-regulate renal TNF- mRNA expression following LPS-induced endotoxaemia. This effect was particularly apparent in the renal medulla. IL-6 mRNA expression in the renal medulla was up-regulated by the agonists whereas plasma, spleen and thymus IL-6 levels were completely inhibited by the agonist, which suggests the existence of tissue specific regulation of IL-6 production in the kidney by ß2-adrenoceptor activation.
Keywords: ß2-Adrenoceptor; IL-6; kidney; rat; TNF-
Correspondence and offprint requests to: Dr Akio Nakamura, Department of Paediatrics, Teikyo University School of Medicine, 2-11-1 Kaga, Itabashi-ku, Tokyo 173, Japan.
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