X. Guirao et al., CATECHOLAMINES INCREASE MONOCYTE TNF RECEPTORS AND INHIBIT TNF THROUGH BETA(2)-ADRENORECEPTOR ACTIVATION, American journal of physiology: endocrinology and metabolism, 36(6), 1997, pp. 1203-1208
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.