Am. J. Respir. Cell Mol. Biol., Vol 10, No. 5, 05 1994, 521-525.
Cytokine-induced interleukin-1 receptor antagonist release in mononuclear phagocytes
CB Marsh and MD Wewers
Division of Pulmonary and Critical Care Medicine, Ohio State University, Columbus.
IL-1ra has recently been shown to suppress both cytokine- and endotoxin-
induced IL-1 beta and TNF-alpha release from monocytes. Given that
mononuclear phagocytes can produce both the proinflammatory cytokines IL-1
alpha, IL-1 beta, and TNF-alpha as well as the suppressive cytokine IL-1ra,
we proposed that IL-1 alpha, IL-1 beta, and TNF-alpha may induce IL-1ra
from mononuclear phagocytes. To test this hypothesis, human mononuclear
cells were stimulated for 18 h with IL-1 alpha, IL-1 beta, or TNF-alpha,
and the supernatants assayed for IL-1ra by ELISA. Each cytokine induced
IL-1ra secretion in a dose-response manner. However, IL-1 alpha and IL-1
beta were better inducers of IL-1ra than was TNF-alpha. IL-1 alpha or IL-1
beta at a dose of 10 ng/ml induced 3 to 6 ng/ml of IL-1ra, while TNF-alpha
at a dose of 100 ng/ml stimulated only 1.4 ng/ml of IL-1ra. This induction
was not due to endotoxin, as all cytokines contained less than 10 pg/ml of
contaminating LPS. Furthermore, for IL-1 beta-induced IL-1ra,
immunoprecipitation of IL-1 beta with an anti-IL-1 beta antibody, but not a
preimmune antibody, blocked the induction of IL-1ra. In contrast to
mononuclear phagocytes, IL-1 alpha, IL-1 beta, and TNF-alpha did not induce
further IL-1ra production in alveolar macrophages. This lack of macrophage
responsiveness may relate to the constitutive production of IL-1ra by these
mature mononuclear phagocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
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Copyright © 1994 American Thoracic Society.
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