Interleukin-6 is the major regulator of acute phase protein synthesis in adult human hepatocytes.
The three monokines interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), and interleukin-6 (IL-6) modulate acute phase plasma protein synthesis in adult human hepatocytes. Only IL-6 stimulates the synthesis of the full spectrum of acute phase proteins as seen in inflammatory states in humans, i.e. synthesis and secretion of C-reactive protein, serum amyloid A, fibrinogen, alpha 1-antitrypsin, alpha 1-antichymotrypsin and haptoglobin are increased while albumin, transferrin and fibronectin are decreased. IL-1 beta as well as TNF alpha, although having a moderate effect on the positive acute phase proteins and inhibiting the synthesis of fibrinogen, albumin and transferrin, fail to induce serum amyloid A and C-reactive protein. These data suggest that IL-6 plays the key role in the regulation of acute phase protein synthesis in human hepatocytes.
Castell
J V
JV
Biochemisches Institut, Universität Freiburg, FRG.
Gómez-Lechón
M J
MJ
David
M
M
Andus
T
T
Geiger
T
T
Trullenque
R
R
Fabra
R
R
Heinrich
P C
PC
D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D000210:Acute-Phase Reaction; D004305:Dose-Response Relationship, Drug; D005340:Fibrinogen / Q000096:biosynthesis; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000494:pharmacology; D015850:Interleukin-6; D007378:Interleukins / Q000502:physiology*; D008099:Liver / Q000502:physiology*; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D000209:Acute-Phase Proteins; D007375:Interleukin-1; D015850:Interleukin-6; D007378:Interleukins; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005340:Fibrinogen