The Journal of Immunology, Vol 150, Issue 9 4001-4007, Copyright © 1993 by American Association of Immunologists

ARTICLES

IL-1 receptor antagonist affects the plasma protein response of Hep 3B cells to conditioned medium from lipopolysaccharide-stimulated monocytes

B Damtew, D Rzewnicki, G Lozanski and I Kushner
Department of Medicine, Case Western Reserve University, MetroHealth Medical Center, Cleveland, OH 44109-1998.

The availability of the IL-1R antagonist (IL-1ra) has made it possible to assess the specific contributions of IL-1 to the acute phase changes induced by complex mixtures of cytokines. We utilized IL-1ra to define the contribution of IL-1 to the effects of conditioned medium from LPS- stimulated monocytes on production of the positive acute phase proteins C-reactive protein, serum amyloid A, fibrinogen, alpha 1-protease inhibitor, complement component C3, alpha 1-antichymotrypsin, alpha 1- acid glycoprotein, and ceruloplasmin and the negative acute phase proteins albumin and transferrin in Hep 3B cells. Induction of C- reactive protein and serum amyloid A was essentially abolished, induction of complement component C3 and alpha 1-acid glycoprotein was moderately decreased and induction of fibrinogen was enhanced. In contrast, there was no significant effect of IL-1ra on induction by conditioned medium of alpha 1-protease inhibitor, alpha 1- antichymotrypsin, or ceruloplasmin. IL-1ra partially blocked the down- regulatory effects of conditioned medium on both of the negative acute phase proteins we studied--albumin and transferrin. These findings enhance our understanding of the contribution of IL-1 to the acute phase response. In addition, they indicate that IL-1ra in vivo may influence synthesis of both positive and negative acute phase proteins.