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Increased Fibrinogen Synthesis in Mice During the Acute Phase Response: Co-Operative Interaction of Interleukin 1, Interleukin 6, and Interleukin 1 Receptor Antagonist
ARMED FORCES RADIOBIOLOGY RESEARCH INST BETHESDA MD
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Interleukin 6 IL-6 stimulates fibrinogen Fg gene expression both in vivo and in vitro while interleukin 1 IL-1 paradoxically stimulates in vivo, yet inhibits in vitro, Fg synthesis. The naturally occurring interleukin 1 receptor antagonist IL-1ra and passive immunization with anti-IL-6 antiserum were used to study the in vivo mechanism of action of IL-1 on Fg gene expression. Changes in plasma FG and hepatic Fg mRNA concentrations were measured following administration of exogenous IL-1ra together with IL-6 or IL-1 to CD2F1 mice. Our results suggest that in vivo, IL-1 per se inhibits Fg production since when IL-14a was co-administered alone. The data suggest that IL-1 stimulates Fg production through intermediate production of IL-6, since stimulation was abrogated when either IL-1ra or anti-IL-6 antiserum was co- administered with IL-1. An in vivo role for IL-1ra in the stimulation of Fg by IL-1 was supported by the observation that within 1 h o IL-1 administration to mice, IL-1ra mRNA was detectable in liver. It appears that IL-1, an early mediator of inflammation, inhibits constitutive expression of Fg genes and stimulates the IL-1ra and IL-6 genes. The inhibitory effect of IL-1 is reversed by endogenous IL-1ra and IL-6 genes. The inhibitory effect of IL-1 is reversed by endogenous IL1ra and by the direct stimulation of Fg gene expression by IL- 6
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