CATECHOLAMINES INCREASE MONOCYTE TNF RECEPTORS AND INHIBIT TNF THROUGH BETA(2)-ADRENORECEPTOR ACTIVATION

Postinjury deficits in monocyte tumor necrosis factor receptors (moTNF R) activity may alter beneficial functions during an inflammatory resp onse. Several counter-regulatory hormones elicited during inflammation may modulate tumor necrosis factor (TNF) activity, but little is know n about their influence on moTNFR. Also, catecholamines inhibit TNF pr oduction, but the adrenoreceptor mechanism of this effect has not been fully clarified. To determine the effect of catecholamines and cortic osteroids on moTNFR, whole blood was coincubated for up to 8 (moTNFR) or 24 h (cytokines) in the presence of lipopolysaccharide (100 ng/ml) and 1) epinephrine (Epi, 10(-6) M), dexamethasone (Dex, 10(-6) M) or b oth (EpiDex, 10(-6) M) to assess the expression of total moTNFR, moTNF R-I, and moTNFR-II. 2) Epi and norepinephrine (EpiNE, 10(-6) M) and th e alpha(1+2)-, beta(1+2)-, beta(1)-, or beta(2)-adrenergic antagonists were used to assess the role of such adrenoreceptors on total moTNFR and TNF production, and N-6,2'-O-dibutyryl adenosine 3',5'-cyclic mono phosphate (DBcAMP) alone or in combination with the phosphodiesterase inhibitor Ro-20-1724/000, to study the cAMP-dependent pathway on total moTNFR. We found that Epi upregulated total moTNFR and moTNFR-II. Dex did not significantly influence total moTNFR or moTNFR-II. Also, EpiN E increased total moTNFR and inhibited TNF by a beta(2)-dependent mech anism. DBcAMP (10(-5) M) modestly enhanced total moTNFR. This suggests a common mechanism for acutely enhancing moTNFR and attenuation of so luble TNF appearance during conditions of severe stress.