Isoproterenol regulates tumour necrosis factor, interleukin‐10, interleukin‐6 and nitric oxide production and protects against the development of vascular hyporeactivity in endotoxaemia

Abstract

SUMMARYPro-inflammatory cytokines, such as tumour necrosis factor ( TNF ) and free radicals, such as nitric oxide ( NO), are mediators of endotoxaemia. Catecholamines are in clinical use to treat the haemodynamic consequences of severe septic shock. Beta-adrenergic agonists exert many of their effects by elevation of intracellular cyclic AMP (cAMP ) concentration. Cyclic AMP can modulate endotoxin-induced cytokine and NO production. Here we investigate the effect of isoproterenol pretreatment on the cytokine and NO production induced by bacterial lipopolysaccharide ( LPS, 4-10 mg/kg). Pretreatment with isoproterenol (10 mg/kg) blunted the LPS-induced TNF response, increased the LPS-induced formation of interleukin-10 and interleukin-6 and reduced the LPSinduced production of NO in conscious mice. In anaesthetized rats, pretreatment with isoproterenol prevented the LPS-induced suppression of vascular contractility to norepinephrine in the thoracic aorta ex vivo. The hyporeactivity is due to expression of the inducible isoform of NO synthase (iNOS) and was restored by in vitro administration of NG-methyl--arginine (-NMA), an inhibitor of NO synthase. However, -NMA did not alter vascular contractility in control vessels or in rings taken from the LPS-treated rats pretreated with isoproterenol. Our findings suggest that, in addition to its haemodynamic actions, isoproterenol may also exert beneficial effects by modulating the endotoxin-induced inflammatory response.

Adrenergic modulation of splenic macrophage cytokine release in polymicrobial sepsis

“…Although our observed lack of effect of IL-10 to attenuate proinflammatory cytokine release is in contrast to previous works, suggesting their physiological actions (37,38), the critical in vivo concentration determining this effect is not known. It can be argued that our ex vivo culture conditions may not accurately represent the in vivo milieu.…”

Suppression of the acute inflammatory response of porcine alveolar‐ and liver macrophages

“…In figure 1 and 2 it is shown that the B-agonists salbutamol and clenbuterol were able to suppress TNF-a release (concentration-dependent) both from alveolar and liver macrophages. These data are in accordance with findings by other researchers using different cell systems (16,19,37). Present data offer additional proof of the potent anti-inflammatory effects of this type of drugs.…”

Salmeterol, a β2-receptor agonist, attenuates lipopolysaccharide-induced lung inflammation in mice

“…Earlier studies have documented the anti-inflammatory effects of ␤-receptor stimulation on the cytokine network. Indeed, ␤-receptor agonists potently inhibited the production of TNF-␣ by monocytes in vitro and in mice and normal humans in vivo (5,32,33,38,42,46). In addition, ␤-receptor stimulation resulted in an enhanced release of the anti-inflammatory cytokine IL-10 in these models (36,38,42,46).…”