IL-1 RECEPTOR ANTAGONIST AFFECTS THE PLASMA-PROTEIN RESPONSE OF HEP-3B CELLS TO CONDITIONED MEDIUM FROM LIPOPOLYSACCHARIDE-STIMULATED MONOCYTES

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 chang es induced by complex mixtures of cytokines. We utilized IL-1ra to def ine the contribution of IL-1 to the effects of conditioned medium from LPS-stimulated monocytes on production of the positive acute phase pr oteins C-reactive protein, serum amyloid A, fibrinogen, alpha1-proteas e inhibitor, complement component C3, alpha1-antichymotrypsin, alpha1- acid glycoprotein, and ceruloplasmin and the negative acute phase prot eins albumin and transferrin in Hep 3B cells. Induction of C-reactive protein and serum amyloid A was essentially abolished, induction of co mplement component C3 and al-acid glycoprotein was moderately decrease d and induction of fibrinogen was enhanced. In contrast, there was no significant effect of IL-1ra on induction by conditioned medium of alp ha1-protease inhibitor, alpha1-antichymotrypsin, or ceruloplasmin. IL- 1ra partially blocked the down-regulatory effects of conditioned mediu m on both of the negative acute phase proteins we studied-albumin and transferrin. These findings enhance our understanding of the contribut ion of IL-1 to the acute phase response. In addition, they indicate th at IL-1ra in vivo may influence synthesis of both positive and negativ e acute phase proteins.