β2-Adrenoceptor agonist suppresses renal tumour necrosis factor and enhances interleukin-6 gene expression induced by endotoxin

Background. beta (2)-Adrenoceptor activation regulates tumour necrosis factor (TNF)-alpha and interleukin-6 (IL-6) production in cultured renal cells. However, it remains uncertain whether, in vivo, the administration of beta (2)-adrenoceptor agonists regulate renal TNF-alpha. and IL-6 mRNA following lipopolysaccharide (LPS) stimulation to cause endotoxaemia. This study was performed in order to evaluate the effect of beta (2)-adrenoceptor agonist on renal TNF-alpha and IL-6 production. Methods. Four-week-old Wistar rats pre-treated with the beta (2)-adrenoceptor agonist terbutaline or formoterol, and/or the beta- and beta (2)-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-alpha and IL-6 mRNA levels and their respective protein release. Results. Administration of beta (2)-adrenoceptor agonists suppressed TNF-x mRNA expression in the whole kidney, by 61% (P < 0.05), as well as plasma, spleen and thymus TNF-a 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 <beta>(2)-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 <beta>(2)-adrenoceptor agonists. beta (2)-Adrenoceptor agonist suppressed LPS-induced TNF-alpha 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. beta (2)-Adrenoceptor agonists down-regulate renal TNF-alpha mRNA expression following LPS-induced endotoxaemia. This effect was particularly apparent in the renaI 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 beta (2)-adrenoceptor activation.