β<SUB>2</SUB>-Adrenoceptor agonist suppresses renal tumour necrosis factor and enhances interleukin-6 gene expression induced by endotoxin

Background. β₂-Adrenoceptor activation regulates tumour necrosis factor (TNF)-α and interleukin-6 (IL-6) production in cultured renal cells. However, it remains uncertain whether, in vivo, the administration of β₂-adrenoceptor agonists regulate renal TNF-α and IL-6 mRNA following lipopolysaccharide (LPS) stimulation to cause endotoxaemia. This study was performed in order to evaluate the effect of β₂-adrenoceptor agonist on renal TNF-α and IL-6 production.
Methods. Four-week-old Wistar rats pre-treated with the β₂-adrenoceptor agonist terbutaline or formoterol, and/or the β- and β₂-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-α and IL-6 mRNA levels and their respective protein release.
Results. Administration of β₂-adrenoceptor agonists suppressed TNF-α mRNA expression in the whole kidney, by 61% (P&lt;0.05), as well as plasma, spleen and thymus TNF-α 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 β₂-adrenoceptor agonists, the basal- and LPS-induced IL-6 mRNA levels in the whole kidney were increased 1.6- and 1.2-fold (P&lt;0.05), respectively, by treatment with β₂-adrenoceptor agonists. β₂-Adrenoceptor agonist suppressed LPS-induced TNF-α mRNA expression by 35% (P&lt;0.05) and stimulated LPS-induced IL-6 mRNA expression by 1.5-fold (P&lt;0.05) in the medullary region of kidney.
Conclusions. β₂-Adrenoceptor agonists down-regulate renal TNF-α 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 β₂-adrenoceptor activation.