INHIBITION OF THE ACUTE-PHASE RESPONSE IN-VIVO BY ANTI-GP130 MONOCLONAL-ANTIBODIES

The acute-phase response is believed to be an important systemic defen ce reaction to inflammation during infection, trauma, injury or neopla sia. Although the interleukin-6 (IL-6) family of cytokines appear to b e the major regulators of the acute-phase reaction, the exact biologic al significance of this process remains unknown. In this study, a pane l of monoclonal antibodies (Mabs) was raised against the extracellular domain of human gp130 (the common signal transducing chain of the IL- 6 cytokine family) in order to inhibit the biological activity of IL-6 -like cytokines in vivo. Mabs designated 4B11 and 2H4 were most effect ive in the inhibition of the in vitro acute-phase response on hepatoma cells and prevented the IL-6-induced growth inhibition of A375 cells. Administration of the antibodies to dogs at a dosage of 8 mg/kg/d sho wed that 2H4 was a potent inhibitor of the IL-6-induced (40 mu g/kg/d) acute-phase response, abrogating IL-6-mediated increments in fibrinog en, C-reactive protein and the platelet count. This antibody, the firs t described to abrogate the acute-phase response in vivo, may not only permit development of a new antiinflammatory strategy, but provides a n excellent tool for defining the function of acute-phase proteins in inflammation and infection.