Production of IL-1 receptor antagonist by hepatocytes is regulated as an acute-phase protein in vivo

Citation
C. Gabay et al., Production of IL-1 receptor antagonist by hepatocytes is regulated as an acute-phase protein in vivo, EUR J IMMUN, 31(2), 2001, pp. 490-499
Citations number
31
Categorie Soggetti
Immunology
Journal title
EUROPEAN JOURNAL OF IMMUNOLOGY
ISSN journal
00142980 → ACNP
Volume
31
Issue
2
Year of publication
2001
Pages
490 - 499
Database
ISI
SICI code
0014-2980(200102)31:2<490:POIRAB>2.0.ZU;2-G
Abstract
IL-1 receptor antagonist (IL-1Ra) is produced by isolated human hepatocytes with characteristics of an acute-phase protein. There are multiple IL-1Ra peptides, one secreted (sIL-1Ra) and three intracellular (icIL-1Ra1, 2, 3). sIL-1Ra, but not icIL-1Ra1, mRNA is transcribed by cultured human hepatocy tes. In this study, we examined in vivo production of IL-1Ra by the liver i n mice in two experimental models of acute-phase response, systemic lipopol ysaccharide (LPS) administration and local turpentine injection. Liver sIL- 1Ra expression was up-regulated in response to both types of stimulation. A fter LPS injection, the hepatic production of sIL-1Ra correlated with the i ncrease in plasma IL-1Ra levels. In addition, the total amount of IL-1Ra pr esent in the liver after LPS injection was six- and tenfold higher than in the lung and spleen. As assessed by in situ hybridization, sIL-1Ra, but not icIL-1Ra, mRNA was produced by hepatocytes in vivo after LPS injection. Us ing IL-6(-/-) mice, we demonstrated that in turpentine-induced inflammation production of IL-1Ra mRNA by the liver is regulated by IL-6. In contrast, local production of IL-1Ra is independent of IL-6. Taken together, these re sults indicate that IL-1Ra is produced by the liver as an acute-phase prote in in vivo.