Differential effect of selective block of α₂-adrenopeceptors on plasma levels of tumour necrosis factor-α, interleukin-6 and corticosterone induced by bacterial lipopolysaccharide in mice

The effect of selective block of α₂-adrenoreceptors on plasma levels of tumour necrosis factor-α (TNF-α), interleukin-6 (IL-6) and corticosterone induced by bacterial lipopolysaccharide (LPS) was investigated in mice using ELISA and RIA. it was found that the LPS-induced TNF-α response was significantly blunted in mice pretreated with CH-38083, a novel and highly selective α₂-adrenoreceptor antagonist (the α₂/α₁ ratio is >2000). In contrast, LPS-induced increases in both corticosterone and IL-6 plasma levels were further increased by CH-38083. Since it has recently been shown that the selective block of α₂-adrenoreceptors located on noradrenergic axon terminals resulted in an increase in the release of noradrenaline (NA), both in the central and peripheral nervous systems, and, in our experiments, that propranolol prevented the effect of α₂-adrenoreceptor blockade on TNF-α plasma levels induced by LPS, it seems likely that the excessive stimulation by NA of β-adrenoreceptors located on cytokine-secreting immune cells is responsible for this action. Since it is generally accepted that increased production of TNF-α is involved in the pathogenesis of inflammation and endotoxin shock on the one hand, and corticosterone and even IL-6 are known to possess anti-inflammatory properties on the other hand, it is suggested that the selective block of α₂-adrenoreceptors might be beneficial in the treatment of inflammation and/or endotoxin shock.