Catecholamines increase monocyte TNF receptors and inhibit TNF through beta 2-adrenoreceptor activation.

Postinjury deficits in monocyte tumor necrosis factor receptors (moTNFR) activity may alter beneficial functions during an inflammatory response. Several counter-regulatory hormones elicited during inflammation may modulate tumor necrosis factor (TNF) activity, but little is known about their influence on moTNFR. Also, catecholamines inhibit TNF production, but the adrenoreceptor mechanism of this effect has not been fully clarified. To determine the effect of catecholamines and corticosteroids 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 both (EpiDex, 10(-6) M) to assess the expression of total moTNFR, moTNFR-I, and moTNFR-II. 2) Epi and norepinephrine (EpiNE, 10(-6) M) and the 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 N6,2'-O-dibutyryl adenosine 3',5'-cyclic monophosphate (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, EpiNE increased total moTNFR and inhibited TNF by a beta 2-dependent mechanism. DBcAMP (10(-5) M) modestly enhanced total moTNFR. This suggests a common mechanism for acutely enhancing moTNFR and attenuation of soluble TNF appearance during conditions of severe stress.