title: Interaction of recombinant IL-1 and recombinant tumor necrosis factor in the induction of mouse acute phase proteins.
abstract: Recombinant mouse and human IL-1 (alpha and beta forms), as well as rTNF-alpha when administered in vivo, induced the production of the mouse acute phase reactants: serum amyloid P-component (SAP), C3, and fibrinogen. The SAP response to all three rIL-1 proteins reached a maximum at a dose of 10(4) U/mouse, which corresponds to 1 to 10 micrograms of protein. The maximum in vivo response consisted of a 10-fold increase in SAP levels, a 2-fold increase in C3 levels, and a 3-fold increase in fibrinogen concentration. By contrast, rTNF-alpha induced a much smaller acute phase (AP) protein response (4-fold increase in SAP) when administered in vivo. Administration of a combination if rIL-1 and rTNF resulted in an AP response that was additive for SAP, synergistic for fibrinogen, but resulted in only the same amount of C3 induced by IL-1 alone. Both recombinant monokines induced new SAP synthesis by isolated hepatocytes in vitro with an optimal response occurring with either 1 U of rIL-1/ml per 2 x 10(5) hepatocytes or 10(-3) U/ml of rTNF. The hepatocyte response to IL-1 was of the same magnitude as the response of intact mice; however, the response to TNF was approximately 10(4) times more efficient in vitro. A mixture of the monokines induced an in vitro SAP response that was additive when suboptimal doses of rIL-1 were combined with optimal amounts of rTNF-alpha. Overall, the findings indicate that both monokines directly trigger hepatocyte synthesis of SAP and that their combined effect probably accounts for a substantial portion of the synthesis of these AP proteins in mice.
mesh_terms: D000209:Acute-Phase Proteins / Q000096:biosynthesis*; D000818:Animals; D003176:Complement C3 / Q000096:biosynthesis; D004357:Drug Synergism; D005260:Female; D007375:Interleukin-1 / Q000494:pharmacology*; D007700:Kinetics; D008099:Liver / Q000166:cytology / Q000378:metabolism; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011994:Recombinant Proteins / Q000494:pharmacology*; D000683:Serum Amyloid P-Component / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D000209:Acute-Phase Proteins; D003176:Complement C3; D007375:Interleukin-1; D011994:Recombinant Proteins; D000683:Serum Amyloid P-Component; D014409:Tumor Necrosis Factor-alpha