DIFFERENTIAL EFFECT OF SELECTIVE BLOCK OF ALPHA(2)-ADRENOCEPTORS ON PLASMA-LEVELS OF TUMOR-NECROSIS-FACTOR-ALPHA, INTERLEUKIN-6 AND CORTICOSTERONE INDUCED BY BACTERIAL LIPOPOLYSACCHARIDE IN MICE

The effect of selective block of alpha(2)-adrenoreceptors on plasma le vels of tumour necrosis factor-alpha (TNF-alpha), 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-in duced TNF-alpha response was significantly blunted in mice pretreated with CH-38083, a novel and highly selective alpha 2-adrenoreceptor ant agonist (the alpha(2)/alpha(1) ratio is >2000). In contrast, LPS-induc ed increases in both corticosterone and IL-6 plasma levels were furthe r increased by CH-38083. Since it has recently been shown that the sel ective block of alpha(2)-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 exp eriments, that propranolol prevented the effect of alpha(2)-adrenorece ptor blockade on TNF-alpha plasma levels induced by LPS, it seems like ly that the excessive stimulation by NA of beta-adrenoreceptors locate d on cytokine-secreting immune cells is responsible for this action. S ince it is generally accepted that increased production of TNF-alpha i s involved in the pathogenesis of inflammation and endotoxin shock on the one hand, and corticosterone and even IL-6 are known to possess an tiinflammatory properties on the other hand, it is suggested that the selective block of alpha(2)-adrenoreceptors might be beneficial in the treatment of inflammation and/or endotoxin shock.