ACTIVATION OF THE ENDOTHELIUM BY IL-1-ALPHA AND GLUCOCORTICOIDS RESULTS IN MAJOR INCREASE OF COMPLEMENT C3 AND FACTOR-B PRODUCTION AND GENERATION OF C3A
M. Coulpier et al., ACTIVATION OF THE ENDOTHELIUM BY IL-1-ALPHA AND GLUCOCORTICOIDS RESULTS IN MAJOR INCREASE OF COMPLEMENT C3 AND FACTOR-B PRODUCTION AND GENERATION OF C3A, Clinical and experimental immunology, 101(1), 1995, pp. 142-149
Constitutive secretion of complement C3 and factor B by the endothelia
l cell (EC) is lowered by therapeutic concentrations of glucocorticoid
s such as hydrocortisone or dexamethasone, whereas regulatory protein
factor H production is increased by these hormones. In contrast, the p
roinflammatory cytokine IL-1 alpha has a stimulatory effect on C3 and
factor B secretion by the endothelium and an inhibitory effect on fact
or H secretion. In this study, we examined the combined effect of IL-1
alpha and glucocorticoids on C3 and factor B expression by the endoth
elial cell. When dexamethasone or hydrocortisone were added to IL-1 al
pha, significant potentialization of IL-1 alpha-induced stimulation of
C3 and factor B production was observed, occurring at various concent
rations of either stimuli. Dose-response experiments indicate that, in
vitro, optimal concentrations are in the range of 10(-7) to 10(-5) M
for dexamethasone and 50-200 U for IL-1 alpha. In contrast, dexamethas
one counteracts, in an additive way, the inhibitory effect of IL-1 alp
ha on regulatory complement protein factor H production by EC. Such a
potentialization between glucocorticoids and IL-1 alpha was not observ
ed for another marker of endothelial activation, IL-1 alpha-induced st
imulation of coagulation tissue factor expression. The association of
glucocorticoids and IL-1 alpha therefore appears to be a specific and
major stimulus for the secretion of complement C3 and factor B, two ac
ute-phase proteins, by the endothelium. As a result of the in vitro en
dothelium stimulation by glucocorticoids and IL-1 alpha, C3a is genera
ted in the vicinity of the endothelial cell. This study further sugges
ts that complement activation, with its deleterious consequences, may
result from the stimulation of endothelium in situations where high le
vels of IL-1 alpha and endogenous glucocorticoids coexist, such as in
septic shock.